Airborne particulate matter (PM) generated by intensive broiler production poses significant risks to poultry respiratory health, yet the molecular mechanisms underlying pulmonary injury remain poorly defined. In this study, PM was collected from a commercial broiler house. Fourteen-day-old AA broilers were exposed to fresh air (control, 0.47 mg·m³), or 4 and 8 mg·m³ total suspended particulates (TSP) for 7 days. iTRAQ-based proteomic profiling identified 4,605 proteins, with 64 differentially expressed (16 upregulated, 48 downregulated) in the high-dose group (8 mg·m³). Enrichment analysis revealed involvement of metabolic pathways, phosphatidylinositol signaling, ATP-binding cassette (ABC) transporters, autophagy, and phagosome-related processes. Key hub proteins-PIK3CD, PIK3C2α, SGK3, and MAP3K20-were highlighted by protein-protein interaction networks and validated by ELISA. Their expression levels correlated significantly with cytokine responses, microbial community shifts, and lung metabolites. RT-qPCR confirmed activation of the MyD88-dependent TLR4/NF-κB and MAPK signaling cascades, along with oxidative stress and apoptotic markers. These findings uncover a PI3K/Akt-centered inflammatory pathway in PM-induced broiler lung injury, offering novel targets for improving poultry respiratory health.