Objective: To explore the effects of rosiglitazone (RSG) combined with insulin (INS) on oxidative stress and lipid profile level in diabetic rats. Methods: 30 healthy male Wistar rats were randomly divided into three groups: healthy control group, DM model group and RSG+INS group, with 10 rats in each group. Diabetic rats were induced by streptozotocin (STZ) model. Then, the rats in RSG+INS group were treated with RSG (3 mg/kg/day) via stomach perfusion and INS (2.25U/kg/day) via hypodermic injection, and administered continuously for 8 weeks. The body weight and blood sugar values of each group were recorded 1 time every 2 weeks. After 8 weeks of drug intervention, the levels of serum total cholesterol(TC), triglyceride(TG), low density lipoprotein (LDL), high density lipoprotein(HDL), glycosylated hemoglobin(HbA1c) and the malonaldehyde(MDA) were detected, and the activities of serum superoxide dismutase(SOD) and glutathione (GSH) were detected. The morphological changes of myocardium were analyzed by hematoxylin alkaline Fuchsin Acid (HBFP) staining. Results: RSG combined with INS treatment in diabetic rats resulted in a time-dependent decrease in blood glucos(P all <0.05). After 8 weeks of drug intervention, the levels of serum TC, TG, LDL, HDL and HbA1c of rats in RSG+INS group were significantly lower than those in DM model group (P all <0.05). Compared with the DM model group, the levels of serum MDA of the rats in RSG+INS group were decreased significantly, while the activities of SOD and GSH were increased significantly (P all <0.05). Compared with the DM model group, the myocardial ischemia/oxygenation in the RSG+INS group was lessened. Conclusions: RSG combined with INS can effectively combat oxidative stress in diabetic rats and improve lipid metabolism in diabetic rats, and it has a protective effect on myocardial tissue. [ABSTRACT FROM AUTHOR]