Abstract: Objective:To observe the effect of Semen Euryales seed coat polyphenols on anti-fatigue,hypoxia tolerance in mice. Methods :Kunming mice were randomly divided into blank group,positive control group(vitamin E,50 mg/kg·d-1),and polyphenols high-dose(400 mg/kg·d-1),medium-dose(200 mg/kg·d-1),lowdose( 100 mg / kg·d-1) group, all mice were administered by intragastric administration, once a day for 5consecutive days. Then,effect of Semen Euryales seed coat polyphenols on mice body weight,weight loading swimming ability,time of bearing hypoxia at normal pressure,hepatic glycogen,muscle glycogen,lactate dehydrogenase,blood urea nitrogen,tissue nitric oxide content and immune organ index. Results:Polyphenols group of high,medium,low dose could extend mice swimming time and hypoxia tolerance time,enhance antistress ability evidently(p<0.05). In addition,activity,appetite,mental state,average daily weight increase and immune organ index were improved. Polyphenols could increase hepatic glycogen,muscle glycogen reserve,serum LDH content,tissue and serum NO content,decrease serum BUN content. Conclusion:Semen Euryales seed coat polyphenols showed the effect of anti-fatigue and enhancing hypoxia tolerance.