Introduction: Considering the antioxidant properties of Otostegia persica extract and role played by antioxidant agents in the improvement of diabetes mellitus, this study investigated the effect of its methanolic extract on serum levels of glucose and lipids in type I diabetic male rats. Materials and Methods: Type I diabetes was induced in male Wistar rats by injection of 70 mg/kg, i.p of streptozotocin. Before and 5 days after injection, fasting blood samples were collected for measurement of glucose and lipids serum levels. Diabetes was confirmed in rats having FBS above 250 mg/dl. Diabetic rats were divided to 15 groups receiving 100, 200 and 300 mg/kg extract, glibenclamide (600 µg/kg) and distilled water (0.5 ml) daily for 3, 6 and 14 days, individually by gavage. Fasting blood samples were collected at the specified time points and serum levels of glucose, cholesterol and triglycerides were measured, using commercial kits by spectrop-hotometery. Results: Treatment of diabetic rats with O. persica extract (100, 200 and 300 mg/kg) for 6 and 14 days and at 300 mg/kg for 3 days significantly decreased glucose serum levels. Also extract at different doses for 3, 6 and 14 days significantly decreased cholesterol and triglycerides serum levels. Extract was more effective than glibenclamide in reducing glucose and triglycerides serum levels in diabetes. Conclusion: Otostegia persica extract has antihyperglycemic and antihyperlipidemic properties in diabetic rats.