【Abstract】Objective To explore the possible mechanism of Xiebaisan in protecting allergic asthma rats from the perspective of host-intestinal flora-metabolism. Methods The SPF SD rats were divided into normal group (NC Group) , model group (M group) and Xiebaisan Group (Xiebaisan Group); Allergic asthma rat model was established by ovalbumin (OVA); The changes of lung histopathology in rats were observed by stained with Hematoxylin-HE. Colon contents were harvested for 16S rRNA high-throughput sequencing to observe the changes of intestinal flora structure and function; Serum and lung tissue samples were collected for non-targeted metabolomics analysis by UHPLC-Q-TOF/MS. Results The results of HE showed that, Xiebaisan group could improve the lung histomorphology of asthmatic rats to some extent compared with M Group; The results of 16S rRNA high-throughput sequencing showed that, the diversity of intestinal flora decreased in M group, and the diversity of intestinal flora was improved in Xiebaisan group compared with M group; The results of serum non-targeted metabolomics test showed that, Xiebaisan group could regulate amino acid metabolism and mTOR pathway, and reversed the differential metabolite expression induced by M group partially; The results of non-targeted metabonomics of lung tissue samples showed that, the Xiebaisan group could regulate carbon metabolism, vascular smooth muscle and cAMP signaling pathways, and reversed the differential metabolite expression induced by M group partially. Conclusion The protective effects of Xiebaisan on allergic asthma in rats may be related to the improvement of the morphological structure of lung tissue, the diversity of intestinal flora, and the regulation of mTOR pathway, Vascular smooth muscle contraction pathway and cAMP pathway, which affect the metabolism of amino acids and carbon.