This study investigates the anti-fatigue effects of Acanthopanax sieboldianus (A. sieboldianus) at various exercise intensities. Two experiments were conducted in 18 Sprague-Dawley rats. In Experiment 1, a three-stage increment test (15 m/min for 5 min, and 20 m/min for 5 min and 25 m/min for 10 min) was performed using a treadmill. In Experiment 2, a 10-min swimming test was conducted. Blood samples were extracted from each rat before, during and after the exercises and the blood concentrations of lactate and glucose measured. In both experiments, water (control) or A. sieboldianus solution (ASS) was administered orally using a zonde 30 min before the exercise. In the swimming test, ASS administration significantly decreased the blood lactate level measured at the end of the exercise and 5 min post-exercise relative to the water group, although the two groups did not differ significantly in the treadmill test. Our study demonstrates that a single oral administration of A. sieboldianus prior to high-intensity exercise significantly decreases the blood lactate concentration suggesting that A. sieboldianus has an intrinsic anti-fatigue effect.