【Abstract】 Background Although mechanical ventilation is an important therapy, it can result in complications. Cellular mechanotransduction of the overstretching stimulus is mediated by means of the cytoskeleton and its cell-cell and cell-extracellular matrix interactions。Objective The aim of this review is to investigate the effect of cytoskeleton and mechanotransduction in the pathophysiology of ventilator-induced lung injury. Content This paper describe the mechanical stimulus of ventilation is translated into an intracellular biochemical signal, inducing endothelial activation, pulmonary vascular permeability and lung injury. The review has been focused on the cytoskeleton and mechanotransduction in the pathophysiology of ventilator-induced lung injury. Trend although the cytoskeleton plays a fundamental role in the pathogenesis of ventilator-induced lung injury, there have been few in vivo studies of alterations in the cytoskeleton and in cytoskeleton-associated proteins during this pathological process, More research on VILI is still worth exploring to meet clinical patients need．