The time course of histopathological changes in a rat lung lavage model of the acute respiratory distress syndrome (ARDS) was analyzed by sacrificing animals 10, 30, 60, 180, and 210 min after the last lung parenchyma lavage which was performed with physiological saline solution. This lavage depleted the lung from its natural surfactant resources leading into a pathophysiological cascade similar to that of the acute respiratory distress syndrome. Tracheotomized rats (12 animals per time point) were pressure-controlled ventilated (Siemens Servo Ventilator 900C) with 100% oxygen at a respiratory rate of 30 breaths/min, inspiration-expiration ratio of 1:2, peak inspiratory pressure of 28 cm H2O at positive end-expiratory pressure (PEEP) of 8 cm H2O. During the whole experimental period, the ventilation was not changed. Blood gases (partial arterial oxygen pressures [PaO2, mmHg] and partial arterial carbon dioxide pressures [PaCO2, mmHg]) were estimated before, directly after, and 10, 30, 60, 90, 120, 150, 180, and 210 min after the last lavage. For grading lung lavage-induced histopathological changes associated with the time-dependent development of ARDS, slides were coded and evaluated without any knowledge of the sacrifice time. A semiquantitative grading was performed with respect to the severity of the following parameters: hyaline membrane formation (HM), interstitial and intraalveolar edema edema (E), and margination and infiltration of polymorphonuclear neutrophil leukocytes (PMNL) into the lung alveoli. The severity of these parameters showed a time-dependent increase after the last lavage. This was accompanied by a time-dependent decrease in partial arterial oxygen pressure (PaO2) values during the early postlavage period (up to 30 min). Thereafter, PaO2 levels remained fairly stable. The severity of intraalveolar and/or perivascular hemorrhages within the lung was not time dependent. The rat lavage model shows similarities to the pathophysiological sequelae occuring during the acute phase of the acute respiratory distress syndrome in humans. Most of the characteristic pathognomic histological changes seen in humans can be observed in this lung lavage model. This ARDS model is brief and easy in its experimental design, showed a good and homogeneous reproducibility of pathophysiological and histopathological parameters, and is therefore a useful model to estimate the influence of therapeutic pharmacological treatments of ARDS.