Abstract: Objective To investigate the changes in bronchial and alveolar epithelial cell apoptosis after mechanical ventilation with different tidal volumes and explore the mechanism and significance of cell apoptosis in ventilation-induced lung injury.Methods Thirty healthy male Sprague-Dawley rats were randomly divided into groups A, B and C to receive tracheotomy under anesthesia for ventilation with different tidal volumes (VT) for 4 h (VT of 10 ml/kg in group A, 20 ml/kg in group B and 40 ml/kg in group C). Lung histopathology was assessed after the ventilation and compared between the 3 groups. The severity of lung injury and bronchial epithelial edema was evaluated, and the extent and location of cell apoptosis in the bronchus and lung tissues were studied by transferase d-UTP end-labeling (TUNEL) assay and immunohistochemistry.Results After mechanical ventilation for 4 h, lung injury and bronchial epithelial edema increased with the increment of VT. By TUNEL assay, the apoptosis index of both alveolar and bronchial epithelial cells was found to increase with VT. Immunohistochemical study identified enhanced caspase-3 expression in the cytoplasm and nuclei of airway and alveolar epithelial cells and vascular endothelial cells in rats with high VT ventilation, and the enhancement was especially obvious in the bronchial epithelial cells. Conclusion Mechanical ventilation with different VTs causes consistent changes in histopathology, cell apoptosis and caspase-3 expression in rats, which support the presumption that cell apoptosis plays an important role in the pathogenesis of high VT ventilation-induced lung injury.