OBJECTIVE - Type 2 diabetic subjects have an increased propensity to premature atherothrombosis. alpha-Tocopherol (AT), a potent antioxidant, has anti-inflammatory properties at high doses, The aim of the Stud was to test the effect of natural (RRR)-AT supplementation (1,200 IU/day) on markers of thrombosis, plasminogen activator ihibitor-1 (PAI-1), and soluble P- selection (sP-selectin) in type 2 diabetic patients with and without macrovascular complications (MVCs) compared with matched control subjects. RESEARCH DESIGN AND METHODS - The volunteers comprised type 2 diabetic patient with (n = 23) and without (n = 24) MVCs and matched control subjects (n = 25) Plasma levels of PAI- 1 and P-selectin were assayed at baseline, after 3 months of supplementation, and after a 2-month washout phase. groups had significantly increased levels of PAI-1 compared with RESULTS-Both diabetic control subjects (P < 0.025), whereas only tape 2 diabetic patients with MVCs had significantly, elevated levels of sP-selectin compared with control subjects. AT supplementation lowered levels of PAI-1 and sP-selectin in all three groups. The reduction in PAI-1 levels with AT supplementation was significantly greater in type 2 diabetic patients with MVCs than in those without MVCs (P = 0.005). CONCLUSIONS - Thus, AT therapy decreases markers of thrombosis in diabetic patients control subjects and could be an adjunctive therapy in the prevention of atherosclerosis.