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Objectives: Wulingsan has been used to cure disease about disorders related to fluid balance for thousands of years. The clinical practice of modern Chinese medicine has found that Wulingsan has the effect on reducing weight and fat, but its mechanism is not clear. This study investigated its effects on obesity rats and explored the underlying mechanisms by analyzing the plasma metabolic profiling. Methods: The effects of Wulingsan on obesity were evaluated with obesity rats induced by high‐fat diet. Ultra high performance liquid chromatography coupled with quadrupole time of flight mass spectrometry (UPLC‐Q‐TOF/MS) was performed to discover potential biomarkers and evaluate whether Wulingsan could regulate these biomarkers. The levels of triglyceride (TG), total cholesterol (TC), high‐density lipoprotein (HDL‐C), and low‐density lipoprotein (LDL‐C) in serum were assessed by ELISA kits. Results: Remarkably, TG, TC, HDL‐C and LDL‐C in obesity rats were ameliorated after oral administration of Wulingsan. Further investigation indicated that the plasma metabolic profiles were clearly improved. Twelve potential biomarkers were identified. After intervention, these biomarkers turned back to normal level at some extent. Conclusion: The results showed that Wulingsan extract groups were normalized. Additionally, this study also showed that the metabonomics method was a promising tool to unravel how traditional Chinese medicines worked and these data can provide scientific basis for clinical application of Wulingsan. [ABSTRACT FROM AUTHOR]