Abstract: OBJECTIVE  To investigate the potential mechanism of platycodon grandiflorum in preventing acute lung injury in mice based on non-target serum metabolomics.METHODS  Twenty-four C57BL/6J mice were randomly divided into control, model, positive and platycodon grandiflorum groups. After 7 days of drug intervention, except for the control group, the other mice were injected with lipopolysaccharide (3 mg·kg^-1) to establish the acute lung injury model and the lung pathology and the expression of inflammatory factors in each group were determined. The serum of mice was collected, and the serum samples were detected by mass spectrometry using GC-MS. The serum metabolic profiles were compared by PCA and Metaboanalyst 5.0 was used to analyze related metabolic pathways.RESULTS  Compared with the control group, the lung pathology of the model group was serious, and the inflammatory factors significantly increased (P < 0.05). Compared with the model group, the pathological conditions of the positive and platycodon grandiflorum groups were improved to some extent, and the inflammatory factors were significantly reduced (P < 0.01). Serum metabolomics results showed that the metabolic profile of the control group and the model group was significantly different, and the metabolic profiles of the positive and platycodon grandiflorum group were close to the normal group.CONCLUSION  Platycodon grandiflorum can improve the inflammation in acute lung injury mice, its potential mechanism may be related to the callback variety of the content of serum metabolites and control multiple metabolic pathways.