The respective roles of high pressure and high tidal volume to promote high airway pressure pulmonary edema are unclear. Positive end-expiratory pressure (PEEP) was shown to reduce lung water content in this type of edema, but its possible effects on cellular lesions were not documented. We compared the consequences of normal tidal volume ventilation in mechanically ventilated rats at a high airway pressure (HiP-LoV) with those of high tidal volume ventilation at a high (HiP-HiV) or low (LoP-HiV) airway pressure and the effects of PEEP (10 cm H2O) on both edema and lung ultrastructure. Pulmonary edema was assessed by extravascular lung water content and microvascular permeability by the dry lung weight and the distribution space of 125I-labeled albumin. HiP-LoV rat lungs were not different from those of controls (7 cm H2O peak pressure ventilation). By contrast, the lungs from the groups submitted to high volume ventilation had significant permeability type edema. This edema was more pronounced in LoP-HiV rats. It was markedly reduced by PEEP, which, in addition, preserved the normal ultrastructural aspect of the alveolar epithelium. This was in striking contrast to the diffuse alveolar damage usually encountered in this type of edema. To our knowledge, this constitutes the first example of a protective effect of PEEP during permeability edema.