Abstract: Objective: Based on metabolomics technology, to clarify the specific endogenous biomarkers and their mechanisms in lung tissues of mice with pulmonary fibrosis. Methods: Sixteen C57BL/6J mice were randomly divided into blank group and bleomycin (BLM) group. A mouse model of pulmonary fibrosis was established. Indicators such as lung function, lung pathology, and hydroxyproline (HYP) levels were detected in each group. Correlation analysis and value evaluation between key differential metabolites and pathological indicators were performed to screen potential biomarkers, followed by functional analysis and pathway enrichment. A multi-layered "biomarker-disease-related target-pathway" interaction network was constructed to clarify the core mechanisms of biomarkers in pulmonary fibrosis. Additionally, qPCR was used to detect the mRNA levels of core targets.Results: Compared with the blank group, mice in the BLM group showed significant reductions in body weight and lung function (P<0.01), accompanied by disordered lung tissue structure, damaged alveolar walls, and increased lung coefficient and lung tissue collagen levels (HYP) (P<0.01). Metabolomics results revealed altered metabolic profiles in mice with pulmonary fibrosis, with differential metabolites primarily enriched in the arachidonic acid metabolism pathway. Correlation analysis and value evaluation of the top 10 significant differential metabolites identified 8 biomarkers significantly associated with pulmonary fibrosis characteristics (P<0.05). The multi-layered interaction network indicated that the core mechanisms of these biomarkers in idiopathic pulmonary fibrosis (IPF) mainly involve inflammatory responses and cell proliferation. qPCR results showed that 6 core targets were significantly upregulated in lung tissues of mice with pulmonary fibrosis (P<0.05, P<0.01).Conclusion: The metabolic profile of mice with pulmonary fibrosis is altered. Biomarkers such as Capryloylglycine, S-(PGA1)-glutathione, Corticosterone, Thymidine, 3-Oxotetradecanoic acid, 3-Hydroxybutyric acid, Uridine, and 3-Hydroxysebacic acid may play important roles in the progression of IPF by regulating inflammatory responses and cell proliferation through targets including IL6, EGFR, CXCL8, MMP9, PTGS2, and MAPK3.