Background and Objective: Fatigue is a complex physiological phenomenon in daily life, which can easily evoke physical dysfunction and serious illness. Asiatic acid with multifaceted biological activities has been used in food and medicinal fields for a long period. The purpose of this study was to explore the potential anti-fatigue effect and mechanisms of asiatic acid in high-intensity exercise. Materials and Methods:The exercise-fatigue model was constituted via a forced swimming test. The experiment mice were continuously fed with asiatic acid for 28 days. The exhaustive time, fatigue relevant biochemical indices, inflammatory cytokines, oxidation parameters and energy metabolism indicators were detected to explore evidence of asiatic acid in high-intensity exercise. Results:Current researches showed that asiatic acid significantly prolonged swimming exhaustive time. In high-intensity exercise, asiatic acid dramatically alleviated fatigue relevant biochemical indices, including CK, LDH, AST, ALT, SUN and BLA to protect against organ injury. Moreover, asiatic acid relieved TNF-alpha and IL-6 levels to restrain inflammatory reaction. In muscle tissue, asiatic acid markedly elevated SOD, CAT and GSH-Px activities to promote antioxidant ability and observably alleviated MDA level to eliminate oxidative injury. Asiatic acid remarkably increased SDH and Na+-K+-ATPase activities to ameliorate energy metabolism. In addition, asiatic acid markedly activated PGC-1 alpha,TFAM, NRF-2 and HO-1 expression to increase energy metabolism and suppress oxidative stress in excessive exercise. Conclusion:These results suggested asiatic acid could improve exercise-induced fatigue via inhibition of inflammatory response, prevention of oxidative stress damage and improvement of energy metabolism in mice. Asiatic acid could serve as a novel potential candidate to postpone fatigue.