Macrophage　polarization　is　modulated　by　many　different　stimuli.　However,　the　effect　of　fibrotic　extracellular　matrix　(ECM)　on　macrophage　polarization　remains　unclear.　In　this　study,　a　mouse　model　of　radiation　induced　pulmonary　fibrosis　(RIPF)　was　established.　Alveolar　macrophages　(AMs)　were　seeded　on　separated　decellularized　ECM　respectively　derived　from　early　RIPF　lung　tissue　(dECM-RIPF)　and　normal　lung　tissue　(dECM-Nor),　on　which　the　polarization　of　AMs　was　examined.　By　way　of　bio-AFM　analysis,　a　significant　difference　in　surface　roughness,　but　no　difference　in　stiffness,　was　found　between　dECM-RIPF　and　dECM-Nor.　Compared　with　dECM-Nor,　dECM-RIPF　induced　a　higher　M1　activation　and　increased　the　levels　of　TNF-alpha,　IL-6　and　IL-18,　while　it　showed　no　significant　effect　M2　density.　Nevertheless,　such　effects　induced　by　dECM-RIPF　could　be　abrogated　by　the　integrin　pan-inhibitor.　Furthermore,　dECM-RIPF　caused　integrin-dependent　activation　of　NFcB,　and　NFcB　inhibitor　was　capable　of　inhibiting　dECM-RIPF-induced　AMs　proliferation　and　M1　activation.　Animal　experi-ments　showed　that　NFcB　inhibitor　alleviated　RIPF　mainly　through　inhibiting　M1　activation　and　down-regulating　the　levels　of　inflammatory　cytokines.　Our　results　showed　that　differential　biophysical　signaling　from　the　fibrotic　ECM　of　early　RIPF　promoted　AMs　polarization　towards　a　M1　phenotype　via　integrin-NFcB.　Inhibition　of　M1　activation　may　be　an　attractive　approach　for　treating　RIPF.