Objective:To establish the lung blast injury model in mice, detect the proteomic changes of lung in mice at different time points, and explore the mechanism of lung blast injury.Methods:A total of 60 healthy male C57BL/6 mice were randomly (random number) divided into the control group, 12-h group after thorax blast, 24-h group, 48-h group, 72-h group and 1-week group ( n=10 each group). Experiments were carried out in the animal laboratory of the General Hospital of the Northern Theater Command. The model of lung blast injury in mice was established by using a self-developed precision blast device, and the lung tissue injury situation was evaluated by gross observation and HE staining. The proteins in mouse lung tissue were quantitatively analyzed based on LC-MS/MS proteomic technology, and the differentially expressed proteins were screened. On this basis, bioinformatics tool was used to analyze proteomic changes. Results:After lung blast injury, scattered bleeding spots could be observed on the surface of lung tissue of mice, and the bleeding points were gradually increased with time, showing a patchy distribution, and the symptoms were the most severe at 24 h. The results of HE staining showed that the normal tissue structure of alveoli disappeared at 12 and 24 h under light microscopy with diffuse bleeding in the alveolar cavity, infiltration of a large number of inflammatory cells, increased interstitial exudate, thickened alveolar wall, and collapsed and merged alveolar cavity. A total of 6 861 proteins were identified by LC-MS/MS in lung tissue samples of mice after thorax blast, and 608 differentially expressed proteins were quantified, of which 227, 140, 202, 258 and 71 differential proteins were at 12 h, 24 h, 48 h, 72 h, and 1 week, respectively. According to GO analysis, 130 biological process subtypes including cell adhesion, extracellular matrix tissue and collagen fibril tissue were obtained. Besides, 66 cellular component involving extracellular exosomes, extracellular matrix and cytoplasm were obtained. And 43 molecular functional subclasses such as extracellular matrix structure composition, actin binding and antioxidant activity were obtained. KEGG analysis yielded 24 pathways including ECM-receptor interactions, focal adhesions and PI3K-Akt signaling pathway across the endothelium.Conclusions:Differentially expressed protein combinations are also different at different time points in the early stage after lung blast in mice, and the injury mechanism is complicated. The lung blast injury is the most serious at 12-24 h after blast and produces significant inflammatory response.