Recent research suggests that reactive oxygen species (including free radicals) may be involved in the initiation and development of vascular complication in diabetics. Free radicals meet many of the criteria required for a role in the pathogenesis of diabetic vascular disease: they are present in tissues affected by the diabetic process, they have a direct toxic effect on tissues, under certain condition glucose molecules can induce free radicals production. Diabetes mellitus represents a state of increased oxidative stress which is based on evidence of increased peroxidation, glycoxidation and reduced antioxidant reserve. Glycative stress can be modified by reducing glycemia, maintaining good diabetic control, and identifying the patients in whom diabetes or impaired glucose tolerance has not been diagnosed. Strategies for reducing the oxidative stress may include the supplementation of antioxidant micronutrients (vitamins E and C, beta-carotene). At present the most appropriate dose, form, method and site of administration of antioxidants are not known. One interesting therapeutic approach for the future will be to make apo-B particles more resistant to oxidative modification or to reduce the prooxidant activity in general.