Abstract: OBJECTIVE To optimize the C57BL/6J diabetic mice model induced by streptozotocin(STZ). METHODS Different diabetic mice model were established with different doses of STZ intraperitoneal administration (180 mg·kg^-1 single dose and 275 mg·kg^-1 averaged by 5 d, 55 mg·kg^-1 each day) and 4-week high-fat diet combined with different doses of STZ(50 mg·kg^-1 single dose, 100 mg·kg^-1 single dose, 150 mg·kg^-1 single dose and 200 mg·kg^-1 for two times at 72 h intervals). Fasting blood glucose, weight, water-drinking and food-consumption were determined, the modeling rate and stability of each group were compared. RESULTS Diabetic model induced by STZ 180 mg·kg^-1 single dose, four weeks high-fat diet combined with STZ 150 mg·kg^-1 single dose or 200 mg·kg^-1 for two times administration were more stable in the long run. CONCLUSION STZ 180 mg·kg^-1 single dose is a suitable type 1 diabetic model, meanwhile, four weeks high-fat diet combined with STZ 150 mg·kg^-1 single dose or 200 mg·kg^-1 for two times administration are appropriate type 2 diabetic model.