Progressive pulmonary fibrosis is a devastating consequence of many acute and chronic insults to the lung. Lung injury leads to alveolar epithelial cell (AEC) death, destruction of the basement membrane and activation of TGFβ. There is subsequent resolution of the injury and a coordinated and concurrent initiation of fibrosis. Both of these processes may involve activation of similar intracellular signaling pathways regulated in part by dynamic changes to the extracellular matrix. Matrix signaling can augment the pro-fibrotic fibroblast response to TGFβ. However, similar matrix/integrin signaling pathways may also be involved in inhibition of ongoing TGFβ-induced AEC apoptosis. Focal adhesion kinase (FAK) is an integrin associated signaling molecule expressed by many cell types. We utilized mice with AEC-specific FAK deletion to isolate the epithelial aspect of integrin signaling in the bleomycin model of lung injury and fibrosis. Mice with AEC-specific deletion of FAK did not exhibit spontaneous lung injury but did have significantly greater TUNEL-positive cells (18.6 vs 7.1) per 200x field, greater BAL protein (3.2 vs 1.8 mg/mL) and significantly greater death (77% vs 19%) after bleomycin injury compared to littermate control mice. Within primary AECs, activated FAK directly associates with caspase8 and inhibit activation of the caspase cascade resulting in less apoptosis in response to TGFβ. Our studies support a model in which dynamic changes to the extracellular matrix after injury promotes fibroblast activation and inhibition of epithelial cell apoptosis in response to TGFβ through FAK activation potentially complicating attempts to non-specifically target this pathway for anti-fibrotic therapy.