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Objective Hypoglycemic Ziyabiti Tablets (HZT) is a traditional multicomponent treatment for diabetes in Xinjiang Uyghur Traditional Medicine.The present study aimed to investigate the effect of HZT in diabetic rats and its activity in cultured liver cells to investigate the relative mechanisms.Methods 10 days high-fat diet fed rats were intraperitoneally injected with alloxan (ALX) at next two subsequent days to induce diabetes mellitus (DM).Then were divided into 5 groups:saline,positive DM control and DM groups treated with different doses of HZT.Fasting blood glucose (FBG),total cholesterol (TC),total triglycerides (TG),high-density lipoprotein (HDL-C),fasting insulin (FI),insulin secretion (IS) and insulin sensitivity index (ISI) were measured.The IC50 of HZT in L-02 cells was determined by MTT assay,in intact and in paracetamol-induced liver injury (Par),on lactate dehydrogenase (LDH) activity and on glucose consumption.Results HZT decreased FBG and TC (P ＜0.05),increased IS (P ＜0.05) and at 440 mg · kg-1 · d-1 increased FI (P ＜ 0.01).In vitro,HZT at 0.1,0.2,and 0.4 mg/mL decreased LDH activity and promoted glucose consumption.Conclusion The hypoglycemic mechanism of HZT is possibly related to increased insulin secretion from the pancreas and increased utilization of glucose by the liver.