ObjectiveTo evaluate the influencing factors and explore a better method of making rat model of type 2 diabetes by high fat and sugar diet and streptozotocin(STZ) injection. MethodsSixty SPF grade of 6 weeks male SD rats were fed with high fat and glucose diet by 4 weeks and then randomly divided into 3 groups, the control group rats(n=20) were injected citric acid by 50 mg/kg and fed with normal diet, and the diabetes mellitus group rats were further divided into 2 subgroups by the different doses of STZ:the rats of diabetes mellitus model group 1(n=20) were injected by 50 mg/kg, while the rats of diabetes mellitus model group 2(n=20) were injected by 35 mg/kg. The diabetes mellitus model group rats were fed with high fat and glucose diet continually. The fasting blood glucose(FBG) were measured on day 3, 7, 10, and 14, respectively. The success model rate(blood glucose > 16.7 mmol/L after 14 days) and the mortality rate were calculated. Meanwhile fasting serum insulin level(FSI), total serum cholesterol(TC), and triglyceride(TG) were measured. ResultsCompared with the control group, the levels of FBG, FSI, TC, and TG were increased significantly in the diabetes mellitus model group 1 and 2(P < 0.05). And insulin sensitivity was worsen markedly(P < 0.05). But the diabetes mellitus model group 2 had higher success rate of making model(85% vs. 75%) and lower mortality(0 vs. 25%), P < 0.05. ConclusionRat model of type 2 diabetes induced by 4 weeks of high fat and sugar feeding and 35 mg/kg STZ injection has high morbidity, strongly security, and stable features.