Patients with diabetes mellitus have an increased risk of premature atherosclerosis, which may be due in part to increased oxidizability of low-density lipoprotein (LDL). Numerous studies have shown that alpha-tocopherol can reduce the oxidative susceptibility of LDL in normoglycemic subjects; however, there are few studies in persons with diabetes. In addition, alpha-tocopherol may reduce the extent of protein glycation. Therefore, the objective of the present study was to assess the effect of RRR-alpha-tocopheryl acetate supplementation on LDL oxidizability and protein glycation in persons with diabetes without evidence of vascular disease. Twenty-eight persons with insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM) were randomly assigned to receive either placebo or 1632 mg (1200 IU) RRR-alpha-tocopherol/d, as tocopheryl acetate, for 8 wk. Plasma and LDL antioxidant concentrations and LDL oxidizability were assessed at both 0 and 8 wk. Plasma and LDL concentrations of alpha-tocopherol were significantly increased in the supplemented group only. Compared with the placebo group, the alpha-tocopherol-supplemented group had significant reductions in LDL oxidizability at 8 wk, as shown by the time-course curves of conjugated diene and lipid peroxide formation. Also, alpha-tocopherol supplementation produced a significant prolongation in the lag phases of both assays, which was evident in both the NIDDM and IDDM subgroups. However, there were no significant changes in glycated hemoglobin or in glycated plasma proteins after alpha-tocopherol supplementation. Thus, alpha-tocopherol supplementation may be beneficial in reducing LDL oxidizability in patients with diabetes.