Background: Vitamin E isomers may protect against atherosclerosis. The aim of this study was to compare the effects of supplementation with either ␣-tocopherol (␣T) or mixed tocopherols rich in ␥-tocopherol (␥T) on markers of oxidative stress and inflammation in patients with type 2 diabetes. Methods: In a double-blind, placebo-controlled trial, 55 patients with type 2 diabetes were randomly assigned to receive (500 mg/day) (a) ␣T, (b) mixed tocopherols, or (c) placebo for 6 weeks. Cellular tocopherols, plasma and urine F 2 -isoprostanes, erythrocyte antioxidant enzyme activities, plasma inflammatory markers, and ex vivo assessment of eicosanoid synthesis were analyzed preand postsupplementation. Results: Neutrophil ␣T and ␥T increased (both P <0.001) with mixed tocopherol supplementation, whereas ␣T (P <0.001) increased and ␥T decreased (P <0.005) after ␣T supplementation. Both ␣T and mixed tocopherol supplementation resulted in reduced plasma F 2 -isoprostanes (P <0.001 and P ؍ 0.001, respectively) but did not affect 24-h urinary F 2 -isoprostanes or erythrocyte antioxidant enzyme activities. Neither ␣T nor mixed tocopherol supplementation affected plasma C-reactive protein, interleukin 6, tumor necrosis factor-␣, or monocyte chemoattractant protein-1. Stimulated neutrophil leukotriene B 4 production decreased significantly in the mixed tocoph-