Abstract: The purpose of this study was to explore the mechanism of Sanzi Yangqin decoction (SYD) from the perspective of hypothalamic metabonomics to prevent the development of prehypertension (PHT) and excessive phlegm-dampness syndrome in rats. WKY rats were randomly divided into a normal group, a model group and a SYD group. The high-fat + high-salt method was used to induce PHT and excessive phlegm-dampness syndrome in the model and SYD rats. Different doses of SYD were used as an intervention over 8 weeks. Food consumption, weight, height, blood lipid and blood pressure were recorded for each group. The results show that, compared with the model group, the diet, weight and blood pressure of rats in SYD group decreased. Metabolites in the hypothalamus which differed in their expression between the three groups were identified and analyzed by LC-MS and the metabolic pathways were then determined. Fourteen metabolites in the hypothalamus were down-regulated and were mainly related to amino acid metabolism, glutathione metabolism, sphingolipid metabolism and glyceride metabolism, suggesting that SYD might alter hypothalamic dietary behavior, thereby affecting amino acid metabolism and energy metabolism. This study was approved by the Animal Ethics Review Committee of Shandong University of Traditional Chinese Medicine (approval number: SDUTCM20211103001).