OBJECTIVE To determine the lung protection of continuous pulmonary artery perfusion with oxygenated blood during cardiopulmonary bypass (CPB). METHODS Thirty patients undergoing mitral valve replacement were randomly divided into the control group (n=15) and the lung perfusion group (n=15). The patients in the lung perfusion group were perfused oxygenated blood continuously to the pulmonary artery during CPB. The patients in the control group were performed the routine procedure of mitral valve replacement. Record the CPB time, aortic cross-clamp time, mechanical ventilation time and ICU monitoring time. The patients' oxygen index (OI) and lung static compliance (Cstat) were measured before the surgery, at 0 h after the CPB and at 0, 6 h after the surgery. Right lung biopsy specimens were obtained at 30 min after the CPB to observe the histological changes. Results The mechanical ventilation time and ICU monitoring time were shorter in the lung perfusion group than those in the control group (P < 0.05). The patients' OI and Cstat were higher after surgery in the lung perfusion group than those in the control group (P < 0.05). Tissue examination showed lung parenchyma edema and inflammatory cells accumulated in the control group, while no remarkable pathological changes occurred in the lung perfusion group. CONCLUSIONS Lung injury exists after the surgery by CPB. Continuous pulmonary artery perfusion with oxygenated blood during CPB can decrease the lung injury.