To explore the mechanism of the core prescription in the treatment of semen non-liquefaction using network pharmacology and molecular docking.Methods:Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and UniProt were used to collect the components and targets of Academician Wang Qi's core prescription.The disease targets were collected by GeneCards and Online Mendelian Inheritance in Man(OMIM)，and then intersected with the drug targets to obtain the core targets.String was used to draw the protein-protein interaction(PPI) network of the core targets.Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis were performed using R language platform to construct the “component-target-disease” map of the core prescription，and the key components were docked with the core targets.Finally，after modeling and drug intervention on rats，enzyme-linked immunosorbent assay(ELISA) was conducted to detect the cytokine level in the prostate of rats in each group，and real-time polymerase chain reaction(RT-PCR) was conducted to detect the expression of IL-17 mRNA，followed by animal experimental validation on core targets and signaling pathways.Results:There were 29 active components in the core prescription，acting on 194 targets，and 24 key components intersected with disease targets，including quercetin，kaempferol and β-sitosterol.The core targets included tumor necrosis factor(TNF),serine protease inhibitor clade E member 1(SERPINE1)，and interleukin-6(IL-6).KEGG enrichment analysis revealed that the core prescription produced effects mainly through AGE-RAGE signaling pathway in diabetic complications and IL-17 signaling pathway.Molecular docking showed that quercetin and β-sitosterol had strong binding activity with the core targets.Additionally，the core prescription reduced the content of TNF，SERPINE1，IL-6，and IL-1β and the expression of IL-17 mRNA in prostate tissue of rats in model group(P<0.01).Conclusion:The key components of Academician Wang Qi's core prescription such as quercetin and β-sitosterol may regulate multiple pathways by acting on targets such as TNF and SERPINE1，and treat semen non-liquefaction via inhibiting inflammatory reaction，resisting oxidation，and regulating fibrin.