Objective To study the influence of Qingzao Runfei Huazhuo Xingxue decoction on pulmonary tissue and lung function in mouse model of lung injury induced by PM2.5, and to provide an idea of clinical prevention and treatment of respiratory diseases induced by PM2.5. Methods Totally 30 clean level male ICR mice were randomly divided into three groups: normal control group, model group and Qingzao Runfei Huazhuo Xingxue decoction intervention group, with 10 mice in each group. Model of PM2.5-induced respiratory disease in mice was reproduced by instilling nasal cavity drip PM2.5 suspension 40 mg/kg once a day for 6 weeks. In the treatment group, the mice were fed with the Qingzao Runfei Huazhuo Xingxue decoction twice a day from the 4th week of instilling PM2.5 suspension until the end of experiment. In the normal control group, the mice were fed as usual. At the end of the experiment, the total protein content in bronchoalveolar lavage fluid (BALF), and lung wet/dry weight (W/D) ratio was determined. Hematoxylin-eosin (HE) staining was used to observe the histopathological changes in lung tissue under light microscope. The inflammatory mediators levels in lung tissue were determined by antibody-sandwich enzyme linked immunosorbent assay (ELISA). Results Respiratory system damage model was successfully reproduced by dripping of PM2.5 suspension in nasal cavity. Compared with normal control group, inflammatory changes and inflammatory cell infiltration in model group were significant, and lung W/D ratio (4.71±0.33 vs. 3.13±0.12), total protein content in BALF (mg/L: 363.98±18.24 vs. 82.13±12.78), tumor necrosis factor-α [TNF-α (ng/L): 185.72±0.23 vs. 31.03±0.16], interleukin-8 [IL-8 (ng/L): 531.85±37.83 vs. 72.64±16.72], and leukotriene B4 [LTB4 (ng/L): 931.74±48.64 vs. 483.81±41.74] in lung tissue were significantly increased (all P < 0.05). Compared with the model group, the inflammatory changes of lung tissue in Qingzao Runfei Huazhuo Xingxue decoction intervention group were significantly reduced, lung W/D ratio (3.92±0.41 vs. 4.71±0.33), total protein content in BALF (mg/L: 213.21±19.62 vs. 363.98±18.24), TNF-α (ng/L: 124.15±0.27 vs. 185.72±0.23), IL-8 (ng/L: 238.42±35.82 vs. 531.85±37.83) and LTB4 (ng/L: 582.85±31.00 vs. 931.74±48.64) levels in lung tissue in Qingzao Runfei Huazhuo Xingxue decoction intervention group were significantly decreased (all P < 0.05). Conclusion Qingzao Runfei Huazhuo Xingxue decoction can improve PM2.5-induced damage and pathological inflammatory changes in lung tissue, which provided some new ideas for the treatment of PM2.5-induced respiratory diseases.