Abstract: 【Objective】Based on systematic pharmacology, a network of active compound, target, pathway and disease-related protein of Huangbaishuanghua oral liquid was established to elucidate the molecular mechanism of treatingdiarrhea in calves, and to provide the theoretical basis for research and development of drugs for the prevention and treatment of diarrhea in calves.【Method】According to oral utilization(OB) ≥ 30% and drug-likeness(DL) ≥ 0.18, using traditional Chinese medicine pharmacology(TCMSP) database retrieval and double liquid medium every taste traditional Chinese medicine(Coptidis Rhizoma, Pulsatilliae Radix, Lonicerae Japonicae Flos, Scutellariae Radix, Radix Sanguisorbae and Mume Fructus) of the active compounds and corresponding targets, imported into Cytoscape drawing software to establish active compounds and their corresponding targets interactions network diagram.The target genes of calf diarrhea were retrieved through Gene Cards database, and the intersection of the two was obtained by Venn diagram.The target gene combination of calf diarrhea and Huangbaishuanghua oral liquid was obtained, and then imported into the String database to obtain the network diagram of the interaction of related proteins.The target genes of Huangbaishuanghua oral liquid on diarrhea of calves were imported into DAVID database for GO function enrichment analysis and KEGG pathway enrichment analysis, respectively.【Result】Forty-three active compounds were screened from Huangbaishuanghua oral Liquid, corresponding to 131 related target genes, respectively.Huangbai Shuanghua Oral Liquid and calf diarrhea intersection protein-protein intera-ction network diagram includded 128 nodes and 205 relationship, among them, serine/threonine protein kinase 1(AKT1), interleukin 2(IL-2) and interleukin 6(IL-6) and interleukin 8(IL-8), promote the mitogen activated protein kinase 1(MAPK1) and aspartic acid with cysteine proteinase 3(CASP3) had high occurrence frequency.The GO function enrichment analysis of the proteins at the intersection target of Huangbaishuanghua oral liquid and diarrhea of calfs was conducted using DAVID database.Finally, 204 GO functional items(FDR< 10^-2) were enriched, including 8 cell composition items, 12 molecular function items and 184 biological process items.The related proteins of Huangbaishuanghua oral liquid in the treatment of diarrhea in calves were mainly enriched in 19 signaling pathways(FDR< 10^-2).【Conclusion】Huangbaishuanghua oral liquid mainly use quercetin, β-phytosterol, stigstanol and kaempferol from Coptidis Rhizoma, Pulsatilliae Radix, Lonicerae Japonicae Flos, Scutellariae Radix, Radix Sanguisorbae and Mume Fructus.Through ATK1, MAPK1, IL-2, IL-6 and IL-8 and other targets, it can play antibacterial and anti-inflammatory roles, inhibit cell damage and regulate immunity through Toll-like receptor signaling pathway, NOD receptor signaling pathway, T cell receptor signaling pathway and B cell receptor signaling pathway, to achieve the purpose of treating calf diarrhea.