Oxidative stress in unilateral ureteral obstruction (UUO) contributes to the development of glomerular and tubulointerstitial lesions. The present study investigated whether oxidized low-density lipoprotein (oLDL) contributes to the pathogenesis of kidney injury in UUO, and whether α-tocopherol modulates such cytotoxicity and promotes repair. Male Sprague-Dawley rats weighing 100–125 g were assigned to three groups of 6 animals each: (1) sham, regular chow; (2) UUO, regular chow; and (3) UUO, α-tocopherol supplementation. We found a significant increase in the level of oxidative stress in the UUO group as measured by malondialdehyde (MDA) content in both plasma and kidneys. The LDL isolated from this group was cytotoxic to rat mesangial cells. The level of oxidation and cytotoxicity was significantly reduced when animals were treated with α-tocopherol. Plasma cholesterol concentration, kidney MDA, and transforming growth factor β1 mRNA expression were all significantly increased in the UUO animals, and partially reduced in α-tocopherol-treated animals. Our data suggest that oxidative modification of LDL is associated with the renal injury in UUO. Taken together, our data support the concept that α-tocopherol can modulate LDL oxidation and its cytotoxic effects on rat mesangial cells in vitro.