The development of various forms of lung injury with increasing tidal volume in normal rats.

•No lung injury occurs in rats ventilated with VT’s <3.5 times the eupneic VT (7.5 ml/kg).•VT’s ∼3.7 times eupneic VT cause failure of extra-alveolar vessels and interstitial edema.•Endothelial-epithelial failure and alveolar edema occur with VT’s ∼4.5 times eupneic VT.•With alveolar edema there are small airway damage, mechanical alterations, and inflammation.•Mechanical changes are good evaluators but bad predictors of fluid accumulation in the lung.