Alpha-tocopherol is a well-known lipophilic-free radical scavenger that is mainly localized in biomembranes. In this study, we investigated the changes in the incorporation and utilization of alpha-tocopherol in erythrocyte membranes of streptozotocin-induced diabetic rats and the effects of insulin to control hyperglycemia on these changes. Diabetes was experimentally induced by the injection of streptozotocin (60 mg/kg, i.v.). Blood was collected to determine the concentrations of alpha-tocopherol and its oxidative metabolite (alpha-tocopherolquinone) in plasma or erythrocyte membranes after streptozotocin injection. In streptozotocin-induced diabetic rats, alpha-tocopherol concentrations were decreased in erythrocyte membranes and increased in plasma. The ratio of alpha-tocopherol in erythrocyte membranes to that in plasma, which reflects the incorporation of alpha-tocopherol into erythrocyte membranes, was dramatically decreased in streptozotocin-induced diabetic rats. Moreover, the ratio of alpha-tocopherolquinone to alpha-tocopherol in erythrocyte membranes, which reflects the utilization of alpha-tocopherol, was increased in streptozotocin-induced diabetic rats. These changes were prevented by insulin to control hyperglycemia. These findings suggest that the abnormalities in the incorporation and utilization of alpha-tocopherol in erythrocyte membranes of streptozotocin-induced diabetes can be restored to normal by insulin therapy to control hyperglycemia.