Previous studies hypothesised that vitamin E could protect against coronary heart disease and vascular complications in diabetes, but no studies have been performed regarding its eventual effects on fibrinolysis. Nevertheless, in Type 2 diabetes mellitus (T2DM) a profound reduction in the fibrinolytic activity has been demonstrated to be involved in vascular complications, probably due to plasminogen activator inhibitor type 1 (PAI-1) overproduction. On this basis we aimed to verify whether an antioxidant treatment with vitamin E is able to lower PAI-1 plasma levels in T2DM. Thirteen T2DM patients (9 males and 4 females; mean age+/-SD, 64.4+/-3.3 yr) were selected through strict admission criteria. These patients were treated with vitamin E (500 IU/die) for 10 weeks. Glyco-lipometabolic, oxidative and haemocoagulative parameters were evaluated at baseline and after 5, 10, 30 and 60 weeks. Vitamin E levels at different times were [median (interquartile range)] 6.1 (5.3-7.7), 8.5 (7.3-9.9), 9.7 (8.9-12.9), 5.6 (4.4-6.8), 5.7 (4.5-7.1) microg/ml, respectively. Significant differences were found for PAI-1 antigen (p=0.006), PAI-1 activity (p=0.028), apolipoprotein B (p=0.015) and antioxidant defence, evaluated as ferric reducing ability of plasma (FRAP) values (p=0.005). Particularly, decrements were detected for PAI-1 antigen between baseline and the 10th week (p<0.05), followed by an increase back to basal at the 30th week. Similar behaviour was found for PAI-1 activity. Regarding the antioxidant defence, FRAP values increased until the 30th week (p<0.05) with a decrease at the 60th week. These results demonstrate that vitamin E is able to lower PAI-1 levels in diabetic patients but this effect does not seem related to improvements of glycometabolic data or to the increase in FRAP values, suggesting that PAI-1 overproduction can be decreased by other effects of vitamin E on endothelial cells.