Considerable evidence indicates that the maintenance of protein redox status is of fundamental importance for cell function, whereas structural changes in proteins are considered to be among the molecular mechanisms leading to diabetic complications. In this study, protein redox status and antioxidant activity were investigated in the lens and vitreous of diabetic and nondiabetic subjects. A significantly lower content of sulphydryl proteins was found in lens and vitreous of diabetic patients than in those of non-diabetic and control subjects. Moreover, an increased formation of protein-bound free sulphydryls and carbonyl proteins, indices of oxidative damage to proteins, was noted in diabetic patients. All these parameters were shown to be altered particularly when diabetes was complicated with retinal alterations. In addition, glutathione peroxidase activity and ascorbic acid levels, known to exert important antioxidant functions in the eye compartment, were found to be significantly decreased in the lens of diabetic patients, especially in the presence of retinal damage. This study indicates an alteration of protein redox status in subjects affected by diabetes mellitus; lens and vitreous proteins were found to be oxidized to a greater extent in the presence of retinal disease, together with a marked decrease of eye antioxidant systems. These results suggest that oxidative events are involved in the onset of diabetic eye complications, in which the decrease in free radical scavengers was shown to be associated with the oxidation of vitreous and lens proteins. Protein oxidation may, therefore, represent an important mechanism in the onset of eye complications in diabetic patients.