[Abstract] Objective: To investigate the therapeutic effect and mechanism of Qingfei Tongluo Formula (QFTLF) on chronic obstructive pulmonary disease (COPD) rats induced by lipopolysaccharide combined with cigarette smoke (LPS+CS). Methods: A COPD rat model was established by intratracheal instillation of LPS combined with CS exposure. Rats were randomly assigned to control, model, aminophylline (0.054 g/kg, 54 mg/kg), and QFTLF low-, medium-, and high-dose (4.59, 9.18, and 18.36 g/kg, respectively) groups. General condition, body weight, and lung function were measured. Lung histopathology and collagen deposition were evaluated by HE and VG staining. Transcriptomic analysis combined with network pharmacology was performed to identify potential targets and signaling pathways involved in the therapeutic effects of QFTLF. For validation, immunofluorescence staining assessed ALOX15 expression and its co-localization with pro-surfactant protein C (Pro-SPC) in lung tissue. Western blot determined the expression of ALOX15, fibrosis-related proteins (α-SMA, Vimentin). In vitro, MLE-12 cells were stimulated with cigarette smoke extract (CSE). Cell viability was evaluated by CCK-8 assay to define optimal conditions for QFTLF-containing serum treatment. Protein levels of ALOX15, TGF-β1, α-SMA, and Vimentin were then assessed by WB. Results: Compared with the controls, model rats showed reduced activity, shortness of breath, slower weight gain (P<0.01). Pulmonary function parameters (Ti, Te, EIP, EEP, and Sr) decreased, whereas Penh increased (P<0.01, P<0.05).. Lung tissues showed marked inflammatory damage and collagen deposition. QFTLF significantly improved these changes. Transcriptomics and network pharmacology analyses identified ALOX15 and the linoleic acid metabolism pathway as potential key targets of QFTLF.. Immunofluorescence and WB validation showed that QFTLF upregulated ALOX15 expression in lung tissue (P<0.01, P<0.05), with co-localization with Pro-SPC. Meanwhile, α-SMA, and Vimentin levels were reduced.. In vitro, QFTLF-containing serum increased ALOX15 expression and decreased TGF-β1, α-SMA, and Vimentin levels in CSE-induced MLE-12 cells (P<0.01, P<0.05). Conclusion: QFTLF alleviates inflammatory injury and fibrosis in COPD rats. These effects may be associated with modulation of the linoleic acid metabolism pathway, upregulation of ALOX15.