Conventional treatments for diabetic retinopathy (DR) includes glycemic control, laser photocoagulation, vitrectomy, intravitreal triamcinolone, and intravitreal anti-vascular endothelial growth factor agents. However these strategies have not proved capable of halting the progression of this disease in all cases. The mechanisms leading to DR are not fully understood, but there is a growing body of evidence showing that oxidative stress plays a pivotal role in the development of this diabetic complication. In fact it has been proposed that oxidative stress is the initial and maintaining event that triggers and provides feedback to the other pathophysiological pathways related to DR. The experimental data discussed in this review show that different antioxidant agents may prevent various biochemical and structural alterations in retinal cells cultured under hyperglycemic conditions, and also in experimental diabetic animals. Although the results of human trials are somewhat variable, some clinical studies have provided promising results.