Increased oxidative stress and impaired antioxidant defense mechanisms are believed to be the important factors contributing to the pathogenesis and progression of diabetes mellitus. In this study, we have reported the effects of the streptozotocin-induced diabetes on the gene expression and the activities of two antioxidant enzymes, manganese superoxide dismutase (MnSOD) and glutathione peroxidase (GPx). We also studied the effects of two antioxidants, vitamin C and DL-alpha-lipoic acid (LA), on the system. Our results showed no significant change in both enzymes activities in diabetic animals compared to controls. Similarly, mRNA and protein profiles of MnSOD showed no change. Though the mRNA expression of GPx did not show any change, Western-blot analysis results demonstrated that protein expression is increased. LA, which is a water- and lipid-soluble antioxidant, decreased the protein expression of MnSOD, though mRNA levels and activities remained unchanged. LA treatment increased the GPx activities in diabetic tissues, significantly, and RT-PCR and Western-blot analysis results demonstrated that this increase in activity is not regulated at the gene level, as both mRNA and protein levels did not change. Supplementing the animals with vitamin C, a powerful water-soluble antioxidant, increased the mRNA expression of MnSOD, though the protein expression and the activity did not change statistically. On the other hand GPx activity increased significantly through post-translational modifications, as both mRNA and protein expressions did not change. These results together with our previous findings about the gene expressions of catalase and Cu-Zn SOD indicate the presence of very intricate control mechanisms regulating the activities of antioxidant enzymes in order to prevent the damaging effects of oxidative stress.