Introduction. Reactive oxygen species play an important role in the pathogenesis of organ damage in diabetes mellitus. Streptozotosin (STZ) is a commonly employed compound to produce diabetes mellitus and these animals exhibit most of diabetic complications. Methods. In our study, diabetes was induced by a single intraperitoneal injection of STZ at a dose of 50 mg/kg in rats and they were killed 12 weeks after STZ. Endogenous lipid peroxide levels, enzymatic and non-enzymatic antioxidants were measured in liver, heart, kidney, brain, and testis tissues to investigate the effect of long-term hyperglycemic state. The susceptibility of diabetic tissues to oxidative stress was also examined in in vitro oxidizing system containing ascorbic acid and iron. Results. We found that prooxidant and antioxidant balance has changed in favor of prooxidation in the tissues of diabetic rats. The susceptibility of liver to oxidative stress increased; however, this susceptibility did not change in heart, kidney, brain, and testis of diabetic rats. Conclusion. Our results indicate that long-term hyperglycemic state disturbs hepatic prooxidant-antioxidant balance at an earlier period and more pronouncedly than other tissues.