Upon inducing acute pulmonary inflammation in a mouse model in which ezrin is selectively knocked out (KO) in monocyte/MΦ, our study uniquely highlights the pivotal role of ezrin for activation of the focal adhesion associated kinase (FAK)/protein kinase B (AKT) axis signaling in lung-recruited monocyte/MΦ, thus promoting their cell adhesion to the lung extracellular matrix (ECM), survival, proliferation, and differentiation. Here, AKT1 is linked to inflammatory response.