A phenylethanoid-rich extract (ECD) of Cistanche deserticola Y.C. Ma, a holoparasitic plant and a valuable traditional Chinese medicine, was evaluated for antifatigue activity in ICR mice. ECD (0.25, 0.50, 1.00 g/kg) was administered orally to mice for 3 weeks. The swimming time to exhaustion was longer in the treatment groups (0.50, 1.00 g/kg) than in the control group (p < 0.01). The serum creatine kinase, lactate dehydrogenase and lactic acid levels were decreased significantly in the treatment groups compared with the control group, while the contents of hemoglobin and glucose were increased significantly. In conclusion, ECD appeared to enhance the swimming capacity of mice by decreasing muscle damage, delaying the accumulation of lactic acid and by improving the energy storage. These results provide scientific evidence for the traditional Chinese medical practice of C. deserticola., ((c) 2009 John Wiley & Sons, Ltd.)