To explore the underlying mechanism of Yulinzhu in improving premature ovarian insufficiency(POI) in rats based on network pharmacology and animal experiments.Methods:Using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)，the active plasma components and predicted targets of five core drugs in Yulinzhu(Cuscutae Semen，Eucommiae Cortex，Rehmanniae Radix Praeparata，Angelicae Sinensis Radix，and Ginseng Radix et Rhizoma) were screened.The corresponding targets of these active components and POI targets were further obtained.Intersection targets were identified using bioinformatics platforms，and a protein-protein interaction(PPI) network was constructed to screen core targets.Gene Ontology(GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis were performed on the core targets using the DAVID database.According to the KEGG pathway analysis results，the hypoxia-inducible factor 1(HIF1) signaling pathway was selected for in vivo validation in animal experiments.Results:The selected core components mainly included quercetin，kaempferol，β-sitosterol，β-carotene，stigmasterol，sesamin，etc.A total of 103 candidate targets related to the disease were identified，with key targets including protein kinase B(AKT1)，caveolin-1(CAV1)，estrogen receptor 1(ESR1)，and Ras homolog family member A(RHOA).These targets were primarily involved in biological processes such as cell proliferation，mediating the biological effects of estrogen，and cell signal transduction.Animal experiments confirmed that Yulinzhu intervention could improve serum hormone levels in POI rats and reduce the protein expression level of HIF1α.Conclusion:Yulinzhu exerts multi-target and multi-pathway effects on POI，and it may improve ovarian function in POI rats through the HIF1 pathway.