Abstract: This study was designed to explore the impact of Huanglian Jiedu Decoction (HLJDT) on macrophage inflammation reaction using the network pharmacology method. Glycolysis, sphingolipid metabolism and glutamine metabolism were also investigated for "multi-component, multi-target and multi-pathway", which supports a foundation for drug innovative research. The TCMSP database was used to screen the active components of HLJDT, the target protein predicted by PharmMapper database and the DAVID database for pathways annotation and analysis. The Cytoscape 3.2.1 software was used to construct the active componenttarget-pathway network map and GENEMANIA database for protein interaction analysis. System Dock Database Site is used in verification of molecular docking. The results showed that 84 active ingredients were screened in HLJDT with a total of 111 target targets. Fourteen pathways are affected according to 13 macrophage-related inflammatory proteins, and 8 pathways including 34 target proteins from glycolysis, sphingolipid metabolism and glutamine metabolism. Inflammation-related proteins and metabolism-related proteins can interact with each other through physical correlation, protein co-expression, etc. Berberine, baicalin and geniposide combined well with 5 important targets. Huanglian Jiedu Decoction may act on the glycolysis and sphingolipid pathways to regulate macrophage inflammatory responses.