The protective activity of the phenylbutazone derivative, sulfinpyrazone on retinal lesions has been assessed in rabbits with severe streptozotocin-induced diabetes. Sulfinpyrazone (8 mg kg-1 per day per os) was administered in diabetic animals in two different experimental procedures: for 135 days in a preventive approach (beginning on the day of initial hyperglicaemia); and for 30 days in a therapeutic approach (beginning on the day of appearance of severe retinal damage). The drug treatment made either with the preventive or the therapeutic approach reduced the incidence of serious retinal lesions and increased that of light lesions as assessed by a biomicroscopic method. Biochemical analyses showed that experimental diabetes was accompanied by sustained decrease in glucose and pyruvate and an increase of the lactate content in the retina. A decrease of alpha-ketoglutarate and citrate and an increase of succinate were also observed along with a decrease of ATP, ADP and an increase in AMP. Either the preventive or the therapeutic approach was followed by an increased pyruvate and ATP content and decreased lactate and AMP content in the retinal tissue. It is possible that this drug acts on the retinal tissue by inhibiting platelet aggregation and protecting vasal endothelium with the consequent suppression of the release of vasoactive substances that facilitate platelet adhesion.