OBJECTIVE Reducing lung injury during cardiopulmonary bypass (CPB) is important for patients' recovery. The present study was designed to evaluate the effects of pulmonary artery perfusion pressure on the extent of lung injury during CPB in an animal model. METHODS Twenty healthy mongrel dogs were randomly divided into four groups, including a control group and three perfusion groups designed to simulate clinical cardiopulmonary bypass-induced lung injury. During pulmonary ischemia and cardiopulmonary bypass, protective perfusions were performed using different perfusion pressures (15-20, 25-30, and 40-45 mmHg), while animals in the control group were not perfused. After pulmonary reperfusion, the changes in pulmonary function and tissue histopathology were determined. RESULTS Compared with the control group, lung compliance, oxygenation and vascular resistance after reperfusion were significantly improved in both low- and moderate-pressure groups. The malonaldehyde concentration, neutrophil sequestration ratio, and expression of ICAM-1 were also decreased significantly in the two groups. However, there were no significant differences in any of these parameters between the control group and the high-pressure group. Histopathological examination demonstrated that there were obvious inflammatory cell infiltration and tissue damage in the control and high-pressure groups, which was prevented in the low- and moderate-pressure groups. CONCLUSIONS The perfusion pressure is an important factor that determines the extent of lung protection, and the use of pressures below 30 mmHg is optimal, with the safest and most effective range being 15-20 mmHg.