The anti-fatigue effect of 50% ethanol extract ([M]) from the dried whole body of Agkistrodon blomhoffii blomhoffii Boie, was investigated using an acute weight-loaded forced swimming (AWLFS) test by monitoring swimming times, blood biochemical parameters, thiobarbiturate-reactive substances (TBARS) as an index of lipid peroxide and antioxidative enzyme activities in blood and tissue. [M] (500 mg/kg/d), given orally for three successive days, significantly prolonged swimming times. It also inhibited the elevation of TBARS in plasma, liver, brain, kidney and soleus, and inhibited the lowering of catalase activity in erythrocyte, liver and soleus. However, it had no inhibitory effect on the elevation of creatine-kinase activity, free fatty acid and lactic acid levels or on the decrease in glucose level in serum. Also, it decreased the plasma TBARS level and increased the superoxide dismutase activity of plasma and erythrocytes in normal rats. From these results, it can be considered that [M] has an anti-fatigue effect.