Two fundamental mechanisms within alveoli are essential for lung function - regulated fluid transport and secretion of surfactant. Surfactant is secreted via exocytosis of lamellar bodies (LBs) in alveolar type II (ATII) cells. We recently described that LB exocytosis results in “fusion-activated Ca²⁺-entry” (FACE) via P2X₄ receptors on LBs. We propose that FACE, in addition to facilitating surfactant secretion, modulates alveolar fluid transport. Correlative fluorescence and atomic force microscopy revealed that FACE-dependent water influx correlated with individual fusion events in rat primary ATII cells. Moreover, ATII cell monolayers grown at air-liquid interface exhibited increases in short-circuit current (I_sc) upon stimulation with ATP or UTP. Both are potent agonists for LB exocytosis, but only ATP activates FACE. ATP, not UTP, elicited additional fusion-dependent increases in I_sc. Overexpressing dominant-negative P2X₄ abrogated this effect by ~ 50%, whereas potentiating P2X₄ lead to ~ 80% increase in I_sc. In a more direct approach, we directly monitored changes in alveolar surface liquid (ASL) on ATII monolayers by confocal microscopy. Only stimulation with ATP, not UTP, led to a significant, fusion-dependent, 20% decrease in ASL indicating apical-to-basolateral fluid transport across ATII monolayers. Finally, our findings were confirmed in in situ measurements of changes in lung compliance upon stimulation of LB fusion and activation of FACE. Our data support the first direct link between LB exocytosis, regulation of surfactant secretion and trans-alveolar fluid resorption via FACE.