The anti-inflammatory mechanism of the leaves of Litchi chinensis Sonn.was studied by network pharmacological analysis and verified by in vitro cell experiments.Methods:The chemical constituents of the leaves of Litchi chinensis Sonn.were searched by literature.The active ingredients of the leaves of Litchi chinensis Sonn.were screened out by a traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP) and the five principles of SwissADME.Each component target was predicted based on Pubchem database and Swiss target prediction database; inflammation genes were obtained from Disgenet database.The intersection target of the component target and inflammatory gene was obtained by Venny2.1.0 database as a potential anti-inflammatory target，and the protein-protein interaction(PPI) network diagram was constructed by inputting the target into STRING 11.0 database.Gene ontology(GO) enrichment analysis and Kyoto encyclopedia of genes and genomes(KEGG) pathway enrichment analysis of anti-inflammatory target genes were conducted by using DAVID 6.8 database.Cytoscape 3.8.0 software was used to construct the network diagram of active ingredients-anti-inflammatory targets-pathways of the leaves of Litchi chinensis Sonn.The effect of alcohol extract of the leaves of Litchi chinensis Sonn.on the activity of RAW264.7 cells was detected by CCK-8 method.The contents of tumor necrosis factor-α(TNF-α）and interleukin-6(IL-6) were detected by enzyme-linked immunosorbent assay(ELISA); the protein expression of cyclooxygenase-2(COX-2) was detected by Western blot.Results:Nine active ingredients were screened from the leaves of Litchi chinensis Sonn.，including 47 potential anti-inflammatory targets，127 GO biological functions，and 68 KEGG signal pathways，involving TNF signal pathway，hypoxia-inducible factor 1(HIF-1) signal pathway，and other inflammation-related pathways.The cell experiments showed that the alcohol extract concentrations of the leaves of Litchi chinensis Sonn.of 12.5，25，and 50 μg/mL displayed no significant cytotoxicity in mouse peritoneal macrophage(RAW264.7).The concentration could reduce the release of TNF-α and IL-6 generated by RAW264.7 cells induced by lipopolysaccharide and inhibit the expression of COX-2 protein.Conclusion:The constructed network diagram of components-targets-pathways reveals that the leaves of Litchi chinensis Sonn.exert anti-inflammatory effects through joint efforts of multi-components，multi-targets，and multi-pathways.The results can provide a theoretical basis for further elucidating the anti-inflammatory mechanism of the leaves of Litchi chinensis Sonn.