Acute lung injury occurs mostly in the very low birth weight and extremely low birth weight infants. The pathological process leading to acute lung injury includes immature and/or diseased lung that experienced oxidative stress, inflammation and mechanical insult with the bronchial, alveolar and capillary injuries and cell death. It may be the first step to the subsequent development of chronic lung disease of prematurity or bronchopulmonary dysplasia. The mechanisms of lung injury are extensively investigated in the experimental models and clinical studies, mostly performed on the adult patients. At present, the explanations of the mechanism(s) leading to lung tissue injury in tiny premature babies are just derived from these studies. Acute lung injury seems to be rather a syndrome than a well-defined nosological unit and is of multifactorial etiology. The purpose of this review is to discuss the main factors contributing to the development of acute lung injury in the very low or extremely low birth weight infants--lung immaturity, mechanical injury, oxidative stress and inflammation. Nevertheless, numerous other factors may influence the status of immature lung after delivery.