To analyze the mechanism of Shenqi Jieyu Formula in the treatment of postpartum depression(PPD) based on network pharmacology and animal experiments.Methods:The TCMSP and Uniprot databases were used to collect the ingredients and targets of Shenqi Jieyu Formula.The targets of disease were then collected from the GeneCards database，and the core targets were obtained by taking the intersection of drug and disease targets.The protein-protein interaction(PPI) network was constructed using the String database.The Metascape platform was used to enrich Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) signaling pathways.Finally，the rats were treated with modeling and drugs and then subjected to open field tests，forced swimming tests，and sucrose water consumption tests，so as to conduct behavioral assessments.The serum IL-1β，IL-6，and TNF-α levels in each group of rats were measured by ELISA.Results:A total of 57 active ingredients of Shenqi Jieyu Formula corresponding to 103 potential targets in the treatment of PPD are screened.The key components are quercetin，β-sitosterol，phytosterols，etc.The core targets involve IL-6，TNF，and IL-1β，which mainly exert their effects through PI3K-AKT，estrogen，T-cell antigen receptor，and other pathways.Animal experiments show that Shenqi Jieyu Formula can increase the horizontal score，vertical score in open field tests，and sucrose water consumption，reduce the immobility time in forced swimming tests，and lower the serum levels of IL-1β，IL-6，and TNF-α in rats.Conclusion:The mechanism of Shenqi Jieyu Formula in the treatment of PPD is characterized by multiple pathways and multiple targets and is related to the immunomodulatory effect of the Shenqi Jieyu Formula.