We examined whether oxidative stress-induced muscle damage occurs during weight-lifting exercise using the rat model. Male Wistar rats were subjected to a single exhaustive session of weight-lifting exercise, and dynamics of blood volume and hemoglobin levels in the exercising muscle were monitored by near-infrared spectroscopy. Total muscle damage was evaluated by the efflux of serum creatine kinase (CK) and uptake of [(3)H]thymidine. The production of reactive oxygen species (ROS) in the muscle was estimated by serial changes in total superoxide dismutase (SOD), glutathione peroxidase (GPX) and catalase (CAT) activities (established indirect markers). Immunohistochemical detection of GPX was also performed. A relatively anoxic state occurred repeatedly after every exercise set in exercising muscle following rapid blood reperfusion and was similar to an ischemia-reperfusion state. Serum CK and mitotic activity in the muscle consistently increased, and damaged muscle fibers that reacted positively to anti-GPX antibody were also observed after exercise. Serial changes in total SOD, GPX, and CAT activities were biphasic and exhibited peaks immediately and 24-72 h after exercise. The first increase was caused by a repeated ischemia-reperfusion-like state following weight-lifting exercise, and the second was dependent on the accumulation of infiltrated phagocytic cells at the damaged portions. These results suggest that ROS-induced muscle fiber damage occurred as a consequence of weight-lifting exercise.