We have shown previously that excessive distention of the rat trachea during mechanical ventilation results in enhanced leukocyte recruitment to the airway. The objectives of this study were to develop a mouse model of PEEP (positive end-expiratory pressure)-induced leukocyte recruitment to the airway and begin to pursue molecular mechanisms that may contribute to the in vivo observation of increased leukocyte adhesion after PEEP exposure. We studied C57Bl/6 wild type mice and mice deficient in p-selectin or intercellular adhesion molecule (ICAM)-1 exposed to intermittent PEEP (8 cm H₂O) applied 5 times for a 1 min duration, at 10 min intervals. After the imposed ventilatory stress, during normal ventilation (0.2 ml / breath, no PEEP), leukocyte adhesion in tracheal post-capillary venules was determined using intravital microscopy. PEEP induced a time-dependent increase in leukocyte adhesion that was significantly increased between 0-60 min (p<0.01). Furthermore, PEEP-induced leukocyte adhesion at 60 min was ablated in p-selectin and ICAM-1 deficient mice. These findings demonstrate the essential nature of both p-selectin and ICAM-1 within airway post-capillary venular endothelium for leukocyte recruitment after airway distension.