Objective:Mechanical ventilation (MV) has long been used as a life-sustaining approach for several decades.However,researchers realized that MV not only brings benefits to patients but also cause lung injury if used improperly,which is termed as ventilator-induced lung injury (VILI).This review aimed to discuss the pathogenesis of VILI and the underlying molecular mechanisms.Data Sources:This review was based on articles in the PubMed database up to December 2017 using the following keywords:ventilator-induced lung injury,pathogenesis,mechanism,and biotrauma.Study Selection:Original articles and reviews pertaining to mechanisms of VILI were included and reviewed.Results:The pathogenesis of VILI was defined gradually,from traditional pathological mechanisms (barotrauma,volutrauma,and atelectrauma) to biotrauma.High airway pressure and transpulmonary pressure or cyclic opening and collapse of alveoli were thought to be the mechanisms of barotraumas,volutrauma,and atelectrauma.In the past two decades,accumulating evidence have addressed the importance of biotrauma during VILI,the molecular mechanism underlying biotrauma included but not limited to proinflammatory cytokines release,reactive oxygen species production,complement activation as well as mechanotransduction.Conclusions:Barotrauma,volutrauma,atelectrauma,and biotrauma contribute to VILI,and the molecular mechanisms are being clarified gradually.More studies are warranted to figure out how to minimize lung injury induced by MV.