Abstract: The objective of present study is to estimate whether the treatment with Viagra in compared to the antioxidative nonenzymatic antioxidant, vitamin E and their synergistic combination would reverse brain disorders of diabetic rats. Animals were divided into two classes, class 1 consists of four normal healthy groups, control (not received any medication) and Viagra, vitamin E and synergistic (Viagra and vitamin E)-treated groups (Gs1, 2, 3 and 4, respectively). Class 2 consists of four diabetic groups injected intraperitoneally with a single dose of alloxane (150 mg kg-1 body weight), diabetic control and diabetic-Viagra, vitamin E and synergistic treated Groups (Gs 5, 6, 7 and 8, respectively). The result revealed that diabetes causes an imbalance in the oxidative state of brain tissue which is confirmed by significant increase in Xanthine Oxidase activity (XO, an enzymes implicated in the production of reactive oxygen and nitrogen species, ROS, RNS, respectively) as well as in nitric oxide (NO, marker of vascular disorder) and malonaldehyde (MDA, index of polyunsaturated fatty acid oxidation) levels with concomitant decrease in the antioxidants, vitamin C and glutathione (GSH) contents. The present investigation also showed that diabetes induces impairment of Adenosine TriphosPhate (ATP) hydrolyzing enzymes, indicated by marked reduction in Na + /K + ATPase activity ,an enzyme responsible for maintaining the ionic gradient necessary for neuronal excitability and stimulation of ectonucleotidases, NTPDases and 5`-nucleotidase, enzymes have a key role in the control of purinergic neuromodulation and neurotransmission. Treatment of diabetic rats with either Viagra or vitamin E significantly improved the diabetic deviation in the above tested parameters. However, administration of the combination of both drugs restored most of these parmeters to near their normal levels. The present data showed that Viagra has a beneficial effect against diabetic brain oxidative stress and related vascular and neuronal complications and its synergistic combination with vitamin E may render it to have an additional potential concern in ameliorating some brain disorders induced by diabetes.