Abstract: The effect of aminoguanidine, nicorandil and their combination against oxidative stress in streptozotocin (STZ) - induced diabetes mellitus was assessed in rats by determining changes in blood glucose level, superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), malondialdehyde (MDA) and nitric oxide (NO) in healthy and experimentally induced diabetic rats. Besides, histhopathological examination of kidney and liver tissues was performed. Diabetic rats were randomized into groups of six rats and received 50mg/kg, intraperitoneally of aminoguanidine (an anti- advanced glycation end products (AGE) which prevents the formation of reactive oxygen species and lipid peroxidation in cells), 0.1mg/kg, orally of nicorandil (nicotinamide derivative which is efficacious in the treatment of hypertension and angina pectoris and a potassium channel opener) and their combination once daily for one month. Blood glucose level was significantly elevated in plasma of diabetic rats. SOD, CAT and GSH levels were significantly reduced, while MDA and NO levels were significantly elevated in plasma of diabetic rats. Abnormalities in both kidney and liver structures of diabetic rats were observed. Treatments of the diabetic rats with aminoguanidine, nicorandil and their combination led to improvement of the abnormalities in SOD, CAT, GSH, MDA, NO and also the histhopathological abnormalities of kidney and liver. From these results it can be concluded that aminoguanidine, nicorandil and their combination have the ability to attenuate oxidative stress induced by streptozotocin. This effect is positively correlated with their anti-oxidant activities.