Background: The most devastating manifestations of diabetes mellitus are vascular complications. Although there are many factors involved in the pathogenesis of diabetic vasculopathy, many studies suggest a role for glucose–induced oxidative stress. Studies in animal models, have demonstrated that the administration of antioxidants restores normal endothelial functions. The study was designed to examine the possible beneficial effects of ascorbic acid, which have antioxidant properties, on vascular permeability in the duodenum of rats with streptozotocin-induced diabetes. Methods: Female adult rats were divided into two control and three diabetic groups. Diabetes was induced by a single injection of streptozotocin (55 mg/kg, ip). One control and two diabetic groups received ascorbic acid in drinking water (800 mg/kg). Diabetic groups received ascorbic acid either as therapeutic for 4 weeks, starting after the induction of diabetes or as combination therapy for 8 weeks starting 3-4 weeks before the induction of diabetes. Vascular permeability was estimated by measuring the extravasations of Evans blue dye and water content of duodenal tissue. Results: As compared to the control group, diabetic animals significantly increased both Evans blue extravasations and water content by 202%. Ascorbic acid, used as treatment or in combination therapy, similarly restored these two variables to normal level. Conclusion: The findings of this study suggest that ascorbic acid might have a role in restoring some dysfunctions of experimental diabetes.