Our underlying hypothesis is that many pathological features of lung disease occur when endogenous capacity of the lung to repair itself following mild to moderate injury is impaired. We use in vivo animal models and in vitro assays to identify putative stem/progenitor cell populations in adult lungs and the microenvironmental cues that modulate their behaviors. We have shown that type 2 alveolar epithelial cells (AEC2) are a major source of new alveolar epithelium in a mouse model of lung growth following pneumonectomy (PNX). To characterize the regenerative niche, we performed single cell RNA sequencing on several cell types following PNX, including CD115+ myeloid cells and Pdgfra+ fibroblasts. We have used in vivo gain and loss of function experiments and in vitro assays to demonstrate that recruited monocytes and alternatively activated macrophages promote the regenerative response post-PNX. We hope that further characterization of the molecular regulation of lung regeneration will identify new cell and molecular therapies to prevent or reverse debilitating pathology in patients with lung disease.