Oxoguanine DNA glycosylase (OGG1) and uracil DNA glycosylase (UDG) are two of the most important repair enzymes that are involved in the base excision repair processes to eliminate oxidative damage from mammalian DNA. Red and white skeletal muscle fibers have very different antioxidant enzyme activity and resistance to oxidative stress. In this paper, we demonstrate that the activity of OGG1, is significantly higher in the red type of skeletal muscle compare to white fibers from old rats. Exercise training (treadmill running, five times per week for eight weeks) resulted in increased OGG1 activity in the nucleus, and decreased activity in the mitochondria of both red and fiber white. The activities of UDG were similar in red and white muscle fibers. Exercise training appears to increase the activity of UDG in the nucleus of red fibers. As well, the activity of UDG was induced in mitochondrial extracts of exercise-trained animals. Taken together, exercise training differently affects the activity of OGG1 in nucleus and mitochondria, suggesting different regulation of the iso-enzymes. In contrast, UDG was accumulated efficiently and showed similar activities in nuclei and mitochondrial extracts of exercise-trained animals. These data provide evidence for differential regulation UDG and OGG1 in maintaining fidelity of DNA in oxidatively stressed cells.