Excess fatigue is a pathological state of continuing accumulation of fatigue, which may cause the deterioration of body health, occurrence of diseases, and even lead to death. A metabonomics study was performed on the excess fatigue rats treated with traditional Chinese medicine Tongxinluo or ginseng based on ultra fast liquid chromatography coupled with ion trap-time of flight mass spectrometry (UFLC-IT-TOF-MS). The plasma metabolic profiling data of the control rats, excess fatigue rats, and excess fatigue rats treated with Tongxinluo or ginseng were acquired. The orthogonal partial least squares analysis (OPLS) was applied for the multivariate statistics and the discovery of important differential metabolites distinguishing the excess fatigue rats treated with Tongxinluo or ginseng from the control rats and excess fatigue rats. The results showed tryptophan, bile acid, lysophosphatidylcholine metabolism were disturbed in the excess fatigue rats. The metabolic pattern including the related metabolic pathways of the rats, being treated with Tongxinluo or ginseng, was adjusted towards the normal state.