To investigate the nephrotoxic effect and related pathway evaluation of Yiguan Decoction on rats using gas chromatography-mass spectrometry(GC-MS) metabolomics method. A blank group, a model group, and a consistently high, medium, and low dose administration group were set up, with rats continuously gavaged for 21 days. GC-MS technology was used to analyze the serum of rats in each group and obtain differential metabolite information. Principal component analysis(PCA) was used to classify the metabolites in the blank group and model group, and the differential metabolites and changes in content in the serum of rats with Yiguan Decoction intervention were searched and analyzed. The results show that pathological sections of the kidneys of rats in the Yiguan Decoction high, medium, and low dose groups show varying degrees of damage. The metabolic profile of the high-dose group rats approach that of the model group. 16 differential metabolites in serum were identified. The three main metabolic pathways involved in the Yiguan Decoction are: biosynthesis of phenylalanine, tyrosine, and tryptophan, sulfur metabolism, and glyceride metabolism.