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BACKGROUND AND OBJECTIVE: Diabetes mellitus is one of the most important risk factors for incidence of nephropathy, retinopathy, neuropathy, and cardiovascular disorders. Use of medicinal plants and their effective constituents for attenuation of hyperglycemia and restoration of lipids to normal level is very important. In this study, the effect of chronic administration of favonoid hesperetin on serum glucose and lipids in diabetic rats was investigated. METHODS: In this experimental study, male Wistar rats (n=40) (250-270 g) were divided into 5 groups, i.e. control, hesperetin-treated control, diabetic, and hesperetin- or glibenclamide-treated diabetic groups. For induction of diabetes, streptozotcin (STZ) was administered (60 mg/Kg i.p.). Hesperetin was administered i.p. at a dose of 10 mg/kg one week after diabetes induction for 6 weeks. Serum glucose, triglyceride, total cholesterol, LDL- and HDL- cholesterol levels were determined before the study, and at 3rd and 6th weeks after the study and compared.FINDINGS: There was a significant reduction in serum glucose level at 3rd and 6th weeks (20.1% and 23.6% respectively) in hesperetin-treated diabetic group as compared to untreated diabetics (p