ABSTRACT: Long term chest blast exposure can lead to mental disorders, brain inflammation and oxidative stress in soldiers. However, the underlying mechanism of brain injury caused indirectly by chest blast remains unclear. It is urgent to find more potential biomarkers to reveal the deeper pathogenesis of this phenomenon. We used iTRAQ labeling combined with LC-MS/MS to screen potential differentially expressed proteins in rat brain after chest blast at different time points. Meanwhile, we also used Go, KEGG, David and Cytoscape to analyze the proteomic profile and explore its pathogenesis. Moreover, Western blotting was used to verify the target proteins. Our data showed that, a total of 6,931 proteins were identified. A total of 255 differentially expressed proteins were identified, of which 43, 84, 52, 97 and 49 proteins were identified from brain tissues at 12h, 24h, 48h, 72h, and 1w after chest blast exposure. Bioinformatics analysis, including GO, COG, KEGG and STRING, further proved that brain damage caused by chest blast exposure was involved in many important biological processes and signal pathways, such as inflammation, cell adhesion, phagocytosis, neuronal and synaptic damage, oxidative stress and apoptosis. Moreover, Western blotting further confirmed that these differentially expressed proteins and signaling pathways were associated with brain damage caused by chest blast exposure. For the first time, we screened and verified the potential protein biomarkers of brain damage caused indirectly by chest blast, and provided a new target for the treatment of this disease.