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 control group and bleomycin model (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 control group, mice in the BLM group showed significant reductions in body mass 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 result 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. 01, P<0. 01, P<0. 05). The multi-layered interaction network indicated that the core mechanisms of these biomarkers mainly involve inflammatory responses and cell proliferation. qPCR result showed that 6 core targets were significantly upregulated in lung tissues of mice with pulmonary fibrosis (P<0. 05, P<0. 01). Conclusions 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 IL-6, EGFR,CXCL8, MMP9, PTGS2, and MAPK3.