Aim: To assess the effect of berberine (BBR) on blood glucose, insulin, lipid profile, oxidative stress and kidney functions in diabetic adult male rats and detect its mechanism(s) of action. Methods: Eighty adult male rats were divided into ten groups. Three experiments were carried out. Experiment I included control group, diabetic control and BBR treated groups (300 mg/kg/day) orally for 1, 2, 4 and 6 weeks. The glucose level, insulin, lipid profile, MDA, TAC, urea and creatinine were measured. Samples from pancreas, liver and kidney were histologically examined. Experiment II: BBR effect after pretreatment with 10% glucose to tongue on vagal nerve activity was recorded. Experiment III: The vagal and sympathetic nerve activity of BBR after administration of atropine, reserpine and propranolol were investigated. Results: Berberine led to significantly decreased glucose level, TC, TG, LDL, MDA, urea and creatinine and significantly increased insulin, HDL and TAC levels after 2 and 4 weeks compared to diabetic control. The histological results confirmed the blood results. Berberine after 10% glucose on the tongue significantly decreased the rate of vagal nerve activity when compared with control and 10% glucose alone. Berberine significantly increased the rate of vagal and sympathetic nerve activity but this rate decreased significantly in pre-treated rats with atropine, prazocine and propranolol when compared to berberine level. Conclusion: Berberine may have antidiabetic effect. Berberine may exert its action on glucose level through inhibition of sweet taste receptors. It can act by activation of the cholinergic receptor, α and β adrenoceptors