Animal model of type 2 diabetes mellitus was induced by high-glucose and high-fat diet combined with low-dose streptozotocin for partial destruction of pancreatic b cells. The rats in model group were intraperitoneally injected with streptozotocin (30 mg/kg) after feeding with high-glucose and high-fat diet for 4 weeks. The value of fasting blood glucose greater than 13.8 mmol/L was 86.7% after the injection for one week, and remained stable in 8 weeks. Glucose tolerance test showed that glucose tolerance was impaired in the model group. The hypoglycemic effect of model group was significant after subcutaneous injection of Exenatide (50 mg/kg), after 3 h the glucose level fell by 38.2% compared with the initial level, showing model rats responded well to Exenatide. The rats were sacrificed to harvest the pancreas for pathological examination in the 13th week, the results showed that part of the islet b cells of model rats was destroyed. The method could be used for pharmacodynamic study in related research.