Ventilator‑associated lung injury (VILI) is a serious complication of mechanical ventilation (MV) in clinic, which threatens the life of patients in severe situation under anesthesia. In recent years, many foreign scholars have found that the uncoupling effect of endothelial nitric oxide synthase (eNOS) is involved in the occurrence and development of VILI. In the view of the mechanism of eNOS uncoupling effect, this review focuses on the effects of eNOS uncoupling on VILI and other similar lung injury, discusses the necessary factors of eNOS uncoupling and the lung environment during the period of peri‑injury reaction, and summarizes the current research advances in uncoupling effect of eNOS in VILI.