A method of high performance liquid chromatography coupled with time-of-flight mass spectrometry was used to detect the endogenous metabolites changes in plasma of normal rats, rats of dampness stagnancy due to spleen deficiency and Astragalus flavone component intervention rats. Metabolism map of rat plasma was obtained and the mechanism of Astragalus flavonoids on dampness stagnancy due to spleen deficiency was studied. Rat model with dampness stagnancy due to spleen deficiency was established by high fat and low protein diet plus load swimming. Liquid chromatography tandem mass spectrometry was used for the analysis of rat plasma sample, and 0.05％ formic acid water with 0.05％ formic acid acetonitrile as the mobile phase was applied in gradient elution with Halo C18 chromatographic column. In this study, partial least squares discriminant analysis and variance analysis were used to screen the potential biomarkers, it was found that the metabolic profile of the Astragalus flavonoids was different from that of the model group, which was close to that of the normal group. A total of 11 potential biomarkers were identified, including glycerol phospholipids, sphingolipids, amino acids, and so on. The metabolic pathways of biomarkers including three tricarboxylic acid cycle, glycerol phospholipid metabolism, fatty acid metabolism, amino acid metabolism and so on, which mainly related to energy metabolism and fat metabolism in the body. Related indexes of rats with syndrome of spleen deficiency of water and dampness were significantly callback after Astragalus flavone intervention, including macro indicators such as body weight, independent activities and micro indicators such as metabolic markers, blood lipids and others. The result showed that Astragalus flavonoids played the role of strengthening the spleen and draining the water mainly through regulating the energy metabolism, fat metabolism and so on.