Objective　To　investigate　the　role　of　macrophages　in　the　process　of　fine　particulate　matter　(PM2.5)　exposure　induced　damage　to　pulmonary　blood-air　barrier.　MGthods　Eighteen　male　BALB/C　mice　(aged　of　10　weeks,　weighing　24　~　27　g)　were　randomly　divided　into　control　group　and　low-　and　high-dose　PM2.5exposure　groups　(receiving　1.　8　and　16.　2　mg/kg,　respectively),　with　6　mice　in　each　group.　The　control　group　received　tracheal　instillations　of　normal　saline　on　days　1,4,　and　7,　whereas　the　exposure　groups　were　administered　corresponding　dose　of　PM2.5exposure　at　the　same　time　points.　In　24　h　after　last　exposure,　pathological　changes　in　the　lung　tissues　were　observed,　and　the　contents　of　total　protein　(TP),　lactate　dehydrogenase　(LDH),　and　alkaline　phosphatase　(AKP)　in　bronchoalveolar　lavage　fluid　(BALF),　and　F4/80　protein　level　in　lung　tissue　were　measured　to　evaluate　the　blood-air　barrier　damage　and　macrophage　infiltration　within　the　lung　tissues.　Additionally,　an　in　vitro　model　of　the　blood-air　barrier　was　established　using　A549　alveolar　epithelial　cells　and　EA.　hy926　vascular　endothelial　cells.　In　combination　with　a　THP-1　macrophage　model,　the　supernatant　PM2.5supernatant,　macrophage　supernatant,　and　PM2.5-macrophage　supernatant　were　incubated　with　the　barrier　model　for　24　h,　respectively.　Transmembrane　electrical　resistance　(TEER),　sodium　fluorescein　permeability　of　the　barrier　model,　and　LDH　release　from　the　barrier　cells　were　measured　to　ascertain　the　extent　of　macrophage-mediated　enhancement　in　barrier　damage　induced　by　PM2.5exposure.　Furthermore,　the　expression　of　inflammatory　cytokines,　such　as　TNF-α,　IL-β,　IL-6,　and　IL-8　in　the　macrophages　after　PM2.5exposure　was　analyzed　with　quantitative　real-time　PCR　(qPCR)　and　enzyme-linked　immunosorbent　assay　(ELISA).　RESULTS　PM2.5exposure　induced　lung　tissue　damage　in　mice　in　a　dose-dependent　manner,　significantly　elevated　the　contents　of　TP,　LDH　and　AKP　in　the　BALF　and　caused　marked　infiltration　of　macrophages　into　the　lung　tissue,　especially　the　high-dose　exposure　when　compared　with　the　mice　from　the　control　group　(P＜0.　01).　In　vitro　barrier　model　exposure　experiments　showed　that　in　comparison　with　the　treatment　of　150　and　300　μg/mL　PM2.5and　macrophage　supernatant,　the　same　doses　of　PM2.5-macrophage　supernatant　resulted　in　notably　decreased　TEER　and　significantly　enhanced　permeability　in　the　barrier　model　(P＜0.　01),　and　markedly　increased　LDH　release　from　epithelial　and　endothelial　barrier　cells　(P＜0.　01).　Additionally,　the　exposure　of　150　and　300　μg/mL　PM2.5led　to　a　significant　up-regulation　of　TNF-α,　IL-lβ,　IL-6,　and　IL-8　in　the　macrophages　(P＜0.　01).　Conclusion　Macrophages　deteriorate　PM2.5-induced　functional　impairment　of　the　pulmonary　blood-air　barrier.　©　2024　Editorial　Office　of　Journal　of　Third　Military　Medical　University.　All　rights　reserved.