Objective:We aimed to reveal the potential active ingredients, targets and pathways of Shiwei Hezi pill (SHP) in the treatment of nephritis based on systematic network pharmacology.Methods:The online database was used to screen the common targets of SHP and nephritis, and the interaction between targets was analyzed. Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed using the Bioinformatics website. Molecular docking was carried out to verify the correlation between core ingredients and key targets. Cytoscape 3.6.1 was applied to perform protein-protein interactions (PPT) network construction and data visualization.Results:A total of 82 active ingredients in SHP were screened, and 140 common targets of SHP and nephritis were obtained. Our results demonstrated that TNF, AKT1 and PTGS2 might be the key targets of SHP in the treatment of nephritis. GO enrichment analysis yielded 2163 GO entries (p< 0.05), including 2,014 entries of the biological process (BP) category, 61 entries of the cell composition (CC) category and 143 entries of the molecular function (MF) category. KEGG pathway enrichment analysis produced 186 signaling pathways (p< 0.05), involving the AGE-RAGE, IL-17and TNF signaling pathways. The results of molecular docking showed that three active ingredients in SHP (quercetin, kaempferol and luteolin) could effectively bind to the TNF, AKT1 and PTGS2 targets.Conclusion:The effective active ingredients in SHP may regulate multiple signaling pathways through multiple targets, thereby exhibiting a therapeutic effect on nephritis.