Abstract:【Abstract】Objective To explore the correlation between age and drug dose during the modeling of diabetic rats. Methods T 100 clean four week old male SD rats were randomly divided into 4-week-old control group, 4-week-old low-dose group, 4-week-old high-dose group, 8-week-old control group, 8-week-old low-dose group and 8-week-old high-dose group. At 4 weeks and 8 weeks, there were 10 rats in the control group and 20 rats in the other model groups. After 4 and 8 weeks of high-fat feeding, STZ low-dose 25 mg/kg and high-dose 40 mg/kg were injected intraperitoneally to establish the model, while the control group was injected with the same amount of citric acid buffer. The modeling rate, mortality, liver function, kidney function and coagulation function of rats in each group on the 6th day after injection were compared. Results There was no significant difference in the modeling rate among the groups (P>0.05), but the mortality of the high-dose group at 4 weeks was the highest, and that of the low-dose group at 8 weeks was the lowest (P<0.001). There were significant differences in serum alkaline phosphatase (AKP), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) between the model group and the control group (P<0.05). The serum AKP, ALT and AST values of low-dose group at 8 weeks were significantly different from those of other models (P<0.05). There was no significant difference in serum creatinine (BUN) and creatinine (BUN) between low dose group and control group (P>0.05). There were significant differences in serum CRE and BUN between 8-week low-dose group and 4-week low-dose and high-dose groups (P<0.05). There was no significant difference in APTT between low dose activated partial thromboplastin group and control group(P>0.05), but there was significant difference between other groups and control group (P<0.05). There were significant differences in APTT between the low-dose group and other models at 8 weeks (P<0.05). The prothrombin time (PT) of high dose group was significantly different from that of normal group (P<0.05). Conclusion The 8 weeks of low dose group showed that the rats had minimal liver and kidney damage after modeling, and coagulation function is not damaged. The 8 weeks of low dose group has the highest survival rate. Therefore, intraperitoneal injection of STZ 25mg/kg after 8 weeks of high-fat feeding is the best model for type 2 diabetes.