Abstract: Using the lipidomics method based on UHPLC-Q-Exactive Orbitrap/MS, the change of phospholipid metabolism in lung tissue of mice induced by lipopolysaccharide (LPS)-induced acute lung injury was analyzed to observe the regulation of abnormal lipids by Jiegeng Decoction and to explore the regulation effect of Jiegeng Decoction on LPS-induced acute lung injury. The lung tissue samples from control group, model group, dexamethasone (positive drug) group, and Jiegeng Decoction group were collected and the lipid components of the sample were extracted. All procedures over mice were performed in accordance with the Guidelines for Care and Use of Laboratory Animals of Nanjing University of Chinese Medicine, and the experiments were approved by the Animal Ethics Committee of our university. The lipidomics technique of UHPLC-Q-Exactive Orbitrap/MS was used to study change of phospholipids in lung tissue of each group. LPS induced acute lung injury in mice with metabolic abnormalities of phospholipids, the specific performance of the PC was significantly upregulated, phosphatidyl ethanolamine (PE), phosphatidyl glycerol (PG), phosphatidyl serine (PS),phosphatidylinositol (PI) and other metabolic disorders, Jiegeng Decoction have a certain role in these phospholipids. LPS-induced acute lung injury caused disturbances of phospholipid in vivo, and Jiegeng Decoction regulates metabolic phospholipids.