Abstract-The anti-fatigue effect of Eucommia ulmoids leaves in mice was studied in this research. Different extracts were prepared: water extract (EUH) and 80% ethanol extract (EUE) of Eucommia ulmoids leaves. The weight-loaded swimming time and biochemical parameters, such as blood lactic acid (LA), serum urea nitrogen (SUN), hepatic glycogen and muscle glycogen were investigated. The results showed that both EUH and EUE exhibited the anti-fatigue effect, but EUE represented more obvious capacity than EUH. In order to learn the mechanism of anti-fatigue effect from Eucommia ulmoids leaves, the hypoxia tolerance test and antioxidation test in vitro were taken. The results showed that compared with control group, EUH or EHE could not prolong the hypoxia tolerance time. However, both EUH and EUE had significant anti-oxidative activity, and antioxidation of EUE was higher than EUH. That meant the anti-fatigue effect of Eucommia ulmoids leaves was related to its anti-oxidative activity.