To explore the mechanism of Eucommia ulmoides Oliv.Leaves in treating osteoporosis based on network pharmacology and molecular docking.Methods:The active components and targets of E.ulmoides leaves were screened by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and SwissTargetPrediction,and the corresponding targets of osteoporosis were searched by GeneCards,Online Mendelian Inheritance in Man(OMIM) and Therapeutic Target Database(TTD).The targets of Chinese herbal medicine and disease were intersected and input into Cytoscape to construct the component-target regulatory network.The protein-protein interaction(PPI) network was constructed by STRING and Cytoscape to screen the core targets.Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) functional enrichment analysis were carried out on the common targets of Chinese herbal medicine and disease,and the signaling pathways related to the common targets were obtained.Finally,AutoDock and Pymol were used for molecular docking between the predicted targets and its corresponding components.Results:After screening,7 active components of E.ulmoides leaves in the treatment of osteoporosis were obtained,and 231 common targets were identified.The mechanism was inferred to be related to NF-κB,MAPK,TNF,PI3K-Akt,IL-17,and HIF-1 signaling pathways,and MAPK1,STAT3,VEGFA,IL6,TP53,EGF,AKT1,JUN,MAPK8,EGFR and TNF genes might play a key role.Conclusion:E.ulmoides leaves may exert the anti-osteoporosis effect by alleviating oxidative stress injury,inhibiting osteoclast formation and promoting osteoblast formation.