Oxygen metabolism is essential for sustaining aerobic life, and normal cellular homeostasis works on a fine balance between the formation and elimination of reactive oxygen species (ROS). Oxidative stress, a cytopathic consequence of excessive production of ROS and the suppression of ROS removal by antioxidant defense system, is implicated in the development of many diseases, including Alzheimer's disease, and diabetes and its complications. Retinopathy, a debilitating microvascular complication of diabetes, is the leading cause of acquired blindness in developed countries. Many diabetes-induced metabolic abnormalities are implicated in its development, and appear to be influenced by elevated oxidative stress; however the exact mechanism of its development remains elusive. Increased superoxide concentration is considered as a causal link between elevated glucose and the other metabolic abnormalities important in the pathogenesis of diabetic complications. Animal studies have shown that antioxidants have beneficial effects on the development of retinopathy, but the results from very limited clinical trials are somewhat ambiguous. Although antioxidants are being used for other chronic diseases, controlled clinical trials are warranted to investigate potential beneficial effects of antioxidants in the development of retinopathy in diabetic patients.