Astragalus membranaceus is a well known oriental medicinal herb. The polysaccharides of the aboveground parts (AMA) and the radix (AMR) of A. membranaceus are the most important functional constituents. Methods and Results: The aim of this study was to determine the effects of AMA and AMR on the oxidative damage induced in the skeletal muscle of rats subjected to exhaustive exercise. Sprague-Dawley rats were randomly divided into exercise and non-exercise groups; in the groups receiving the test compounds, AMA and AMR were administered orally for 30 days. Skeletal muscle samples were collected from each rat after running to exhaustion on a treadmill to determine the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) and the concentation of malondialdehyde (MDA). The antioxidant enzyme activities of SOD and GSH-Px of skeletal muscle of AMA- and AMR-treated groups were significantly higher than those of the control and commercial sports drink (SPD)-treated groups in exhaustive exercise rats. In addition, MDA concentrations in the skeletal muscle of the AMA- and AMR-treated groups were significantly lower than those of the control and SPD-treated groups. In the present study, the effects of AMA and AMR on exercise endurance capacity were also evaluated in mice subjected to a swimming exercise test. AMA and AMR supplementation prolonged the swimming time of mice and enhanced exercise endurance capacity. AMA and AMR possess the ability to retard and lower the production of blood lactate, and prevent the decrease of serum blood glucose. Conclusions: These results showed that, AMR and AMA exerted beneficial effect in mice, increasing the activity of the antioxidant systems and inhibiting oxidative stress induced by exhaustive exercise. The compounds improved exercise performance and showed anti-fatigue effects against exhaustive exercise.