Nonenzymatic glycosylation(NEG) of many protein occurs in diabetes mellitus and it has been suggested that NEG may play a critical role in the long-term tissue complications of diabetes. The inhibiting effect of the antioxidant on protein glycation has been reported recently. This study was performed to evaluate the effect of vitamin E supplementation on protein glycation in non-insulin-dependent diabetes mellitus(NIDDM). Eighteen oral hypoglycemic-reducing NIDDM patients(HbA1C = 6-10%), ages 40-60, were divided into three groups. Two groups of 6 diabetic patients, recieved daily vitamin E supplementation of 1000 IU(Group i) and 2000 IU(Group ii), respectively, for 2 months. A third group of 6 diabetic patients, served as the control group and received placebo(Group iii). Fasting plasma glucose, fasting labile HbA1C, stable HbA1C and fructosamine were measured in the basal state and after 1 and 2 months of treatment. Vitamin E content in serum increased 3.1- and 5.1-fold in group i and group ii after 2 months on vitamin E administration. Fasting plasma glucose did not change HbA1C and stable HbA1C, did not show signigicant changes during the study in group iii. Fructosamine is decreased after 1 and 2 months on vitamin E adminstration. However, labile HbA1C and stable HbA1C showed more decreasing tendency in group I and group ii, is not meaningful in statistical view. These results demonstrate that vitamin E supplementation may suggest the possibility of inhibiting protein glycation in NIDDM patients independently of changes in plasma glucose, an effect that may be due to the inhibition of labile glycosylation. However, vitamin E supplementation do not reduce glycation of protein significantly. Futhermore, long term studies are needed to establish the usefulness of vitamin E supplementation for the prevention of diabetic complications.