【Abstract】Objective To explore the mechanism of ursolic acid against silicosis fibrosis based on network pharmacology, molecular docking and in vitro experiments. Methods The ursolic acid targets were obtained from GeneCards, PubChem and other databases. Disease-related databases (GeneCards, OMIM) were searched for targets related to silicosis fibrosis and epithelial-mesenchymal transition (EMT). The micro-biotech platform was used to screen the intersecting targets, and the protein-protein interaction network was constructed through the String database and Cytoscape to screen the core targets. David database was used for GO and KEGG enrichment analysis. Use AutoDock for molecular docking validation. Validation of key targets by beas-2B cell experiments. Results A total of 179 ursolic acid targets, 8023 and 6809 silicosis fibrosis and EMT-related targets, and 133 intersecting targets were obtained. Nine core targets, including Akt1, STAT3 and MMP9, were screened out, among which MMP9 and Akt1 had the highest connectivity in the PPI network. Molecular docking showed that ursolic acid had strong binding activity with MMP9 (binding energy -8.4 kJ/mol) and Akt1 (binding energy -7.9 kJ/mol). KEGG analysis suggested that the PI3K-Akt signaling pathway was a key regulatory pathway. In vitro experiments showed that ursolic acid significantly inhibited the decrease in cell viability induced by SiO2 (CCK8). Decreased p-Akt expression (Western blot); The expression of the fibrosis marker α-SMA and the interstitial marker Vimentin was down-regulated, while the expression of the epithelial marker E-cadherin (immunofluorescence/Western blot) was up-regulated. Conclusion Ursolic acid may play an anti-silicosis fibrosis role by inhibiting Akt phosphorylation and MMP9 expression and regulating the process of EMT. 【Keywords】ursolic acid; silicosis fibrosis; PI3K/Akt signaling pathway; epithelial-mesenchymal transition; Molecular docking