Abstract: The metabonomics method was used to explore the processing and synergistic mechanism of epimedium fried with suet oil in warming the kidney and enhancing yang. The kidney-yang deficiency rat model was established by injection of hydrocortisone. Then the UPLC-Q-TOF-MS (ultra-performance liquid chromatography with quadrupole time-of-flight tandem mass spectrometry) metabolomics method was combined with multivariate statistical analysis methods and univariate statistical analysis to screen and identify kidney-yang deficiency potential biomarkers in plasma and urine samples. Finally the metabolic regulation mechanism of suet oil group, the epimedium raw product group, the epimedium heating product group, and the epimedium fried with suet oil group improved kidney-yang deficiency was analyzed. The results showed that the plasma and urine metabolism of rats with kidney-yang deficiency induced by hydrocortisone showed obvious trajectory changes. 15 biomarkers related to kidney-yang deficiency were identified in plasma and urine, involving 5 metabolic pathways, namely glycerophospholipid metabolism, sphingolipid metabolism, sulfur metabolism, glyoxylate acid and dicarboxylate metabolism, and cysteine and methionine metabolism. The metabolic pathway of epimedium fried with suet oil warming kidney and promoting yang involved glycerophospholipid metabolism, cysteine and methionine metabolism, and the two processing factors of epimedium fried with suet oil "heating" and "suet oil" enhanced its function of warming the kidney and promoting yang by regulating glycerophospholipid metabolism, cysteine and methionine metabolism, respectively. In this way, the processing and synergistic mechanism of epimedium fried with suet oil was clarified. The animal experiments involved in this article comply with ethical standards and have been approved by the Animal Ethics Committee of Jiangsu Provincial Academy of Chinese Medicine (approval number:AEWC-20200702-119).