Objective To investigate the molecular mechanism of Shema Zhichuan Liquid in the treatment of eosinophilic asthma (EA) based on transcriptomics and network pharmacology. Methods (1) Peripheral blood samples were collected from 10 patients with acute exacerbation of EA (mild to moderate) and 10 healthy control volunteers. Transcriptome sequencing was performed on both groups to construct database for sequencing and identify differentially expressed genes (DEGs) associated with EA. (2) Active components and their targets in Shema Zhichuan Liquid were identified through TCMSP,literature searches,Swiss ADME and Swiss Target Prediction databases. The intersection of DEGs of EA with targets of active components in Shema Zhichuan Liquid yielded key targets for EA treatment. A protein-protein interaction (PPI) network of these key targets was constructed. The core targets were screened according to node-degree values. "Chinese medicine-active ingredients-key targets" network was built to analyze and screen the key active ingredients of Shema Zhichuan Liquid in treating EA. The Metascape platform was used to conduct GO function and KEGG signaling pathway enrichment analysis of key targets. Finally,the binding capability between the core targets and key active components was verified through molecular docking. Results A total of 2109 DEGs,including 922 upregulated genes and 1187 downregulated genes were screened. A total of 102 active ingredients and 826 targets of Shema Zhichuan Liquid were identified. After taking the intersection,74 key targets of Shema Zhichuan Liquid in the treatment of EA were obtained. PPI analysis identified IFNG,PTGS2,MAPK3,CCL2,IL10 and CXCL8 as core targets. "Chinese medicine-active ingredients-key targets" network analysis highlighted quercetin,kaempferol,luteolin,β-sitosterol and stigmasterol as key active components. The key targets were primarily involved in biological processes including inflammatory response,chemotaxis,and cellular response to cytokines stimulus,and the signaling pathways such as PI3K-Akt,MAPK,Toll-like receptor,NF-κB and TNF. Molecular docking indicated β-sitosterol and stigmasterol have strong binding affinities for six core targets,while MAPK3,PTGS2 and CXCL8 showed good binding ability with five key active ingredients. Conclusion The therapeutic effects of Shema Zhichuan Liquid on EA may be mediated through key active components,such as β-sitosterol and stigmasterol,which acted on core targets (MAPK3,CXCL8 and PTGS2)and regulated signaling pathways (PI3K-Akt,MAPK,and NF-κB).