Objective: To investigate the antipyretic mechanism of Herba Ephedrae (Eph)-Ramulus Cinnamomi (RC) herb pair on yeast-induced pyrexia in rats. Methods: Totally 30 qualified male SD rats were randomly assigned to the normal control (NC)group, the pyrexia model (model)group, the Eph, RC and Eph-RC treatmentgroups by a random digital table, 6 rats in eachgroup. Each rat received a 20％ aqueous suspension of yeast (10mL/kg) except the NCgroup. The 3 treatmentgroups were administered 8.1, 5.4 and 13.5g/kg Eph, RC and Eph-RC respectively at 5 and 12h after yeast injection, the NCgroup and the modelgroups were administered equal volume of distilled water. Rectal temperatures were measured at 0, 6, 8, 10, 12, 15, 18, 24 and 30h and urine was collected prior to yeast injection and at 6, 10, 18, 24, 30, and 36h after yeast injection. Then urine metabolomic profiling bygas chromatography tandem mass spectrometry, coupled with multivariate statistical analysis and pattern recognition techniques were used to explore the antipyretic effects of Eph-RC. Partial least squares discriminate analysis was used to analyze the metabolomics dataset including classification and regression in metabolomics plot profiling. Results: Compared with the NCgroup, rectal temperatures were significantly higher in the modelgroup (P＜0.01), while 3 treatmentgroups decreased significantly compared with the modelgroup (P＜0.05 or P＜0.01). Rectal temperatures of Eph-RC-treated rats started togo down at 6h, and markedly decreased at 8, 12, 15, 18 and 24h (P＜0.05 or P＜0.01), while those of the Eph and RCgroups had decreased firstly at 8h and were markedly lower at 12h (P＜0.05 or P＜0.01). Seventeen potential biomarkers related to pyrexia were confirmed and identified, including pyruvic acid, L-phenylalanine, L-tyrosine, phenylacetic acid, hippuric acid, succinic acid, citrate and so on. Eight potential alterations of metabolic pathways including phenylalanine metabolism, citrate cycle, tryptophan metabolism, biosynthesis of valine, leucine and isoleucine, were identified in relation to the antipyretic effects of Eph-RC using MetPA software. Conclusion: The antipyretic effect of Eph-RC herb pair on yeast-induced pyrexia in rats involved correction of perturbed amino acid, fatty acid, and carbohydrate metabolism according to the metabolic pathway analysis with MetPA.