Diabetes mellitus is characterized by complications affecting several organs, including the kidney. Lipid peroxidation increases in diabetes and has been implicated in the pathogenesis of diabetic complications. In this study, we examined the ability of two antioxidants, vitamin E and probucol, to reduce lipid peroxidation in vivo and renal hypertrophy, an early stage of diabetic nephropathy, in rats. Animals were divided into four groups: non-diabetic, diabetic, diabetic treated with vitamin E, and diabetic treated with probucol. Animals were given antioxidants by intraperitoneal injection after induction of diabetes by streptozotocin injection. After 7 wk, lipid peroxidation in vivo was measured by analyzing urinary excretion of lipophilic aldehydes and related carbonyl compounds (LACC) as 2,4-dinitrophenylhydrazones by high-performance liquid chromatography. A number of urinary lipophilic nonpolar and polar aldehydes and related carbonyl compounds were identified, almost all of which increased in diabetes. Antioxidant treatment resulted in significantly decreased excretion of urinary LACC excretion. Antioxidant treatment of diabetic rats reduced renal hypertrophy. There was a high correlation between kidney weight and urinary LACC. Since LACC are accepted markers of lipid peroxidation, these results indicate that antioxidants can reduce the elevated lipid peroxidation of diabetes and may slow the onset of diabetic nephropathy.