Skip to main content

The effects of dosage and the routes of administrations of streptozotocin and alloxan on induction rate of typel diabetes mellitus and mortality rate in rats


The approach and novelty of this scientific work was to formulate the appropriate Streptozotocin (STZ) and Alloxan dosage in different routes of administration to imply minimum mortality rate and high incidence of diabetes mellitus (DM) in the rat experiment model. Rats were randomly divided into STZ, Alloxan and control groups. 1-Alloxan group was divided into two subgroups: intraperitoneal (ip) subgroups which received a single dose of, 140, 120, 100 and 80 mg/kg; and the subcutaneous (sc) subgroups which received a single dose of, 120, 110, 100, 90, and 80 mg/kg. 2-STZ group was divided into four subgroups of ip route. The ip subgroup which received intraperitoneally a single dose of, 30, 35, 40 and 50 mg/kg. 3-The control group: This group received solo distilled water. The injection day was considered as the day zero. Blood glucose levels and mortality rate were recorded. Subsequently, 30 days after, the logistic regression modeling was used to evaluate the effect of the explanatory variables, the dose levels, and route approaches, on the probability of DM incidence, and mortality. According to the statistical logistic analysis for Alloxan, it is concluded that the minimum dosage needed to induce DM was 120 mg/kg by sc method (probability 0.712). In addition, the logistic analysis for STZ showed that the optimal dose-level for STZ was 40 mg/kg with ip with approximate induction of DM probability 0.764. Based on the data, male Wistar rats in which received a single dosage of Alloxan by sc injection at dose of 120 mg/kg showed the most desirable result of induction of type I DM; furthermore, those in which received STZ by ip injection at the dose of 40 mg/kg developed a persistent and optimal DM state characterized by high rate of DM induction and low- level of mortality.


  1. 1.

    TA S. Diagnosis and classification of diabetes mellitus. Diabetes care. 2014; 37: S81.

    Article  Google Scholar 

  2. 2.

    Shaw JE, Sicree RA, Zimmet PZ. Global estimates of the prevalence of diabetes for 2010 and 2030. 2010; 87(1): 4–14.

    CAS  Google Scholar 

  3. 3.

    Agbaje IM, Rogers DA, McVicar CM, McClure N, Atkinson AB, Mallidis C, Lewis SE. Insulin dependant diabetes mellitus: implications for male reproductive function. Hum Repro. 2007; 22(7): 1871–1877.

    CAS  Article  Google Scholar 

  4. 4.

    Etuk EU. Animal models for studying diabetes mellitus. Agric Biol JN A. 2010; 1(2): 130–134.

    CAS  Google Scholar 

  5. 5.

    Federiuk IF, Casey HM, Quinn MJ, Wood MD, Ward WK. Induction of type-1 diabetes mellitus in laboratory rats by use of alloxan: route of administration, pitfalls, and insulin treatment. Comp Me. 2004; 54(3): 252–257.

    CAS  Google Scholar 

  6. 6.

    Awai M, Narasaki M, Yamanoi Y, Seno S. Induction of diabetes in animals by parenteral administration of ferric nitrilotriacetate. A model of experimental hemochromatosis. Am J Patho. 1979; 95(3): 663–673.

    CAS  Google Scholar 

  7. 7.

    Chatzigeorgiou A, Halapas A, Kalafatakis K, Kamper E. The use of animal models in the study of diabetes mellitus. In Vivo. 2009; 23(2): 245–258.

    CAS  PubMed  Google Scholar 

  8. 8.

    Rees DA, Alcolado JC. Animal models of diabetes mellitus. Diabet Me. 2005; 22(4): 359–370.

    CAS  Article  Google Scholar 

  9. 9.

    King AJ. The use of animal models in diabetes research. Br J Pharmaco. 2012; 166(3): 877–894.

    CAS  Article  Google Scholar 

  10. 10.

    Hoftiezer V, Carpenter AM. Comparison of streptozotocin and alloxan-induced diabetes in the rat, including volumetric quantitation of the pancreatic islets. Diabetologi. 1973; 9(3): 178–184.

    CAS  Google Scholar 

  11. 11.

    Gajdosik A, Gajdosikova A, Stefek M, Navarova J, Hozova R. Streptozotocin-induced experimental diabetes in male Wistar rats. Gen Physiol Biophy. 1999; 18: 54–62.

    CAS  Google Scholar 

  12. 12.

    Srinivasan K, Ramarao P. Animal models in type 2 diabetes research: an overview. Indian J Med Re. 2007; 125(3): 451–472.

    CAS  Google Scholar 

  13. 13.

    Ar’Rajab A, Ahren B. Long-term diabetogenic effect of streptozotocin in rats. Pancrea. 1993; 8(1): 50–57.

    Article  Google Scholar 

  14. 14.

    Chougale AD, Panaskar SN, Gurao PM, Arvindekar AU. Optimization of Alloxan Dose is Essential to Induce Stable Diabetes for Prolonged Period. Asian Journal of Biochemistry. 2007; 2(6): 402–408.

    CAS  Article  Google Scholar 

  15. 15.

    Jain DK, Arya RK. Anomalies in alloxan-induced diabetic model: It is better to standardize it first. Indian J Pharmaco. 2011; 43(1): 91.

    Article  Google Scholar 

  16. 16.

    Kalinichev M, Robbins MJ, Hartfield EM, Maycox PR, Moore SH, Savage KM, Austin NE, Jones DN. Comparison between intraperitoneal and subcutaneous phencyclidine administration in Sprague-Dawley rats: a locomotor activity and gene induction study. Prog Neuropsychopharmacol Biol Psychiatr. 2008; 32(2): 414–422.

    CAS  Article  Google Scholar 

  17. 17.

    Inoue Y, Kiryu S, Izawa K, Watanabe M, Tojo A, Ohtomo K. Comparison of subcutaneous and intraperitoneal injection of D- luciferin for in vivo bioluminescence imaging. Eur J Nucl Med Mol Imagin. 2009; 36(5): 771–779.

    CAS  Article  Google Scholar 

Download references


We wish to extend our sincere thanks to the late Mrs. Jamileh Rezaei. This article is financially supported “by research department of the school of medicine” and Vice Chancellors of Research at the Shahid Beheshti University of Medical Sciences, Tehran, Iran (Grants no 1393-1-91-13500).

Author information



Corresponding author

Correspondence to Mohammad Bayat.

Rights and permissions

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Mostafavinia, A., Amini, A., Ghorishi, S.K. et al. The effects of dosage and the routes of administrations of streptozotocin and alloxan on induction rate of typel diabetes mellitus and mortality rate in rats. Lab Anim Res 32, 160–165 (2016).

Download citation


  • Type one diabetes mellitus
  • alloxan
  • streptozotocin
  • intraperitoneal route
  • subcutaneous route
  • rate of diabetes induction