The current study investigated the effect of n-butanol and water fractions of Pedicularis decora Franch on oxidative stress induced by an acute exhaustive exercise. Institute of Cancer Research (ICR) mice were divided into sedentary, exercise and recovery groups. Each group includes control and water fraction as well as n-butanol fraction subgroup. Mice were treated with the two fractions of P. decora Franch root and saline for a period of 21 days. After the treatment period, the exercise and recovery groups swam to exhaust. Sedentary and exercise groups animals were sacrificed immediately after swimming exercise and recovery mice were sacrificed after 24 h. In sedentary group, superoxide dismutase (SOD), glutathione peroxidase (GPx) activities were higher and lipid peroxidation (LPO) levels were lower with the two fractions treatment. SOD, GPx, lactate dehydrogease (LDH) activities and LPO levels significantly decreased in exercise and recovery groups with the two fractions treatment. Also, the two fraction could promote energy deposits through an increase in glycogen contents. In addition, n-butanol fraction significantly prolonged swimming time to exhaustion. In short, n-butanol and water fractions of P. decora Franch may both protect mice against oxidative stress induced by an acute exhaustive exercise and n-butanol fraction could significantly improve the swimming capacity. Further, n-butanol fraction is more pronounced in ameliorating the oxidative stress induced by an acute exhaustive swimming exercise.