Purpose: The purpose of this study was to evaluate the therapeutic potential of oral curcumin (1 g/kg body weight of rat) in the prevention and treatment of streptozotocin-induced diabetic retinopathy in Wistar albino rats. Methods: The treatment was carried out for a period of 16 weeks in diabetic rats and evaluated for hyperglycemic, antioxidant (superoxide dismutase, catalase, and glutathione), and inflammatory parameters (tumor necrosis factor-α, vascular endothelial growth factor). Rat fundus was observed weekly to see any visible changes in the retina, such as tortuosity and dilation of retinal vessels. Histological changes were evaluated by transmission electron microscopy. Results: Treatment with curcumin showed significant hypoglycemic activity compared with the diabetic group. Retinal glutathione levels were decreased by 1.5-fold, and antioxidant enzymes, superoxide dismutase and catalase, showed >2-fold decrease in activity in the diabetic group; on the other hand, curcumin positively modulated the antioxidant system. Proinflammatory cytokines, tumor necrosis factor-α and vascular endothelial growth factor, were elevated >2-fold in the diabetic retinae, but prevented by curcumin. Transmission electron microscopy showed degeneration of endothelial cell organelles and increase in capillary basement membrane thickness in diabetic retina, but curcumin prevented the structural degeneration and increase in capillary basement membrane thickness in the diabetic rat retinae. Conclusion: Based on the above results, it may be concluded that curcumin may have potential benefits in the prevention of retinopathy in diabetic patients.