This study evaluated submicroscopic features of active pleural remodeling associated with chemical pleurodesis. Twenty seven rabbits received intrapleural injection of 0.5% silver nitrate (SN; N = 9) or 400 mg/kg talc slurry (N = 9) in 2 ml of saline solution; control rabbits (N = 9) received 2 ml of saline alone. The rabbits were sacrificed 15 minutes, 24 hours, or 7 days postinjection, and specimens of visceral pleura were obtained, fixed, and photographed for submicroscopic analysis. After 15 minutes of talc or SN exposure, prominent injury to the mesothelial cells and mesothelial cell-mesothelial basement membrane (MC-MBM) union was visible. There was focal remesothelialization of the denuded area through mesothelial cell migration, proliferation, and differentiation. After 24 hours, early wound healing, characterized by a superficial exudate, was evident where myofibroblasts had proliferated through a gap in the MC-MBM. After 7 days, proliferation of highly active myofibroblasts was observed; these cells produced abundant extracellular matrix components in a more organized distribution paralleling the surface. This third stage of remodeling was more evident with SN than talc-induced chemical pleurodesis. Our results suggest that ideal chemical pleurodesis results from injury to the MC-MBM union and abnormal wound healing, involving three essential steps: remesothelialization, fibroblastic proliferation, and extracellular matrix accumulation and remodeling.