Backgrolnd: It has been proposed that the oxidative stress may play a crucial role in the development of chronic diabetic comp1ications. The oxidative modification has been suggested as a common process invo)ved in a variety of protein damages observed in the diabetic comptications. But, there has been no direct evidence demonstrating the oxidative modifications of proteins in the disease. Methods: we measured the carbonyl group content of hepatic cytoselic proteins as well as blood glycohemog- lobin in the control and in the chronic diabetic rats. Diabetes was induced by streptbzotocin injection (65 mg/kg, I.p.) and maintained for 8 weeks with or without vitamin treatments. Vitamins E and C were employed to investigate the effects of antioxidants on the oxidative modifications of proteins in diab0tes. Results: The glycohemoglobin was markedly in- creased in the diabetic group (14.8+-0.3%) compared to the age-matched control group (4,3+-0.2%). The carbonyl group content, an index of oaxidized protein, of the hepatic cytosolic protein was also significantly higher in the diabetic group than in the contxol graup (2.17+-0.17 vs. 1.44+-0.07 nmo)es/mg protein; p<0.05). Dietary vitamin C for 7 weeks did nof effect either carbonyl group content or glycohemoglobin. However, vitamin E effectively prevented the oxidation of protein (1.67+-0.10 nmoles/mg protein) without affecting the glycohemoglobin percentage considerably (12.4+-0. 4%). Conclusion: The current data clearly demonstrates that the hepatic intracellular proteins are oxidatively modified in the chronic diabetes and that the hyperglycemia itself might not be the cause of the modification. Such oxidative changes of intracelluiar protein, coald be prevented by the adminislration of vitamin E.