Lepidium meyenii. Walp. (maca), a Peruvian plant, has been utilized in the Andean region as a food and a medicine for centuries. This study was carried out to investigate the anti-physical fatigue effect of polysaccharides from maca (MCP) and the possible mechanisms. Mice were administered daily doses of 500, 1000 and 2000 mg/kg MCP for 28 days. After the treatment period, the anti-fatigue effect of MCP were evaluated by exhaustive swimming exercise and several biochemical parameters related to physical fatigue were determined: blood lactic acid (BLA), serum urea nitrogen (SUN), glycogen, superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), and malondialdehyde (MDA). Results showed that MCP could prolong exhaustive swimming times, decrease the levels of BLA and SUN, and increase the liver glycogen contents. Furthermore, MCP increased activities of SOD, GPx and CAT, and decreased MDA level. The present findings indicate that MCP has obvious anti-physical fatigue effect, and the possible mechanisms were to delay the increase of BLA, reduce the catabolic decomposition of protein for energy and lipid peroxidation, and improve reserve and antioxidant enzymes activities.