BACKGROUND Pulmonary artery perfusion during cardiopulmonary bypass (CPB) is a novel adjunctive method, which can minimize the lung ischemic-reperfusion injury and inflammatory response. This study evaluated the protective effect of pulmonary perfusion with hypothermic HTK solution in corrections of congenital heart defects with pulmonary hypertension. METHODS Between June 2009 and December 2009, 24 consecutive infants with congenital heart defects and pulmonary hypertension were randomly divided into perfused group (n = 12) and control group (n = 12). Oxygen index, alveolar-arterial O2 gradient, serum levels of malondialchehyche (MDA), interleukin (IL)-6, -8, -10, soluble intercellular adhesion molecule-1 (sICAM-1), and P-selectin were measured before commencement and serially for 48 hours after termination of bypass. RESULTS Oxygenation values were better preserved in the perfused group than in the control group. The serum levels of IL-6 increased immediately after CPB in both groups and returned to baseline at 48 hours after CPB,but it was restored faster and earlier in the perfused group. The serum levels of IL-8, sICAM-1, and MDA remained at baseline at each point after CPB in the perfused group and elevated significantly immediately after CPB in the control group, except for sICAM-1. The serum level of IL-10 increased immediately after CPB and decreased to baseline at 48 hours after CPB in both groups, but the IL-10 level in the perfused group was significantly higher than in the control group at 12 hours after CPB. The serum P-selectin levels in the control group immediately after CPB were significantly higher than prebypass levels. Moreover, there were no significant differences in postoperative clinical characters, except for the intubated time. CONCLUSIONS In infants with congenital heart defects, pulmonary perfusion with hypothermic HTK solution during cardiopulmonary bypass could ameliorate lung function and reduce the inflammatory response.