Aim To observe the effects of ulinastatin (UTI) on the level of matrix metalloproteinase-9 on plasma in patients receiving cardiac valve replacement therapy and to investigate the protective effects of Ulinastatin on lung injury. Methods 40 adult patients, ASA score Ⅱ～Ⅲ, scheduled for elective cardiac valvular replacement, were randomly allocated into two groups, Ulinastatin group (group U, n=20) and control group (group C, n=20). Group U in which patients received a total of 12 ku/kg of ulinastatin. 6 ku/kg ulinastatin was given a IV bolus on introduction of anesthesia and before CPB. Group C received an equal amount of isotonic sodium chloride solution. Blood samples were taken from radial artery before introduction of anesthesia, 10 min after initiation of CPB, 30 min after initiation of CPB, 1 h, 3 h and 6 h after CPB for determination of plasma matrix metalloproteinase-9 concentrations. VD/VT and alveolar-arterial oxygen A-aDO2 were checked before introduction of anesthesia, 1 h, 3 h, 6 h after initiation of CPB studied after CPB. Results There was no significant difference between two groups in age, weight, operation time, CPB time, and aortic cross-clamping time. Compared with those before introduction of anesthesia, the concentrations of matrix metalloproteinase-9 increased significantly at 10 min after initiation of CPB to 6 h after initiation of CPB in two groups (P<0.05). And no difference between two groups before introduction of anesthesia. The concentration of VD/VT at 1 h after initiation of CPB to 6 h after initiation of CPB increased significantly (P<0.05). The concentrations of MMP-9 at 10 min after initiation of CPB to 6 h after initiation of CPB, VD/VT A-aDO2 at 1 h after initiation of CPB to 6 h after initiation of CPB in ulinastatin group was lower than those in control group significantly (P<0.05). Conclusions Ulinastatin suppressed the excessive release of matrix metalloproteinase-9 and protected lung injury in patients undergoing cardiopulmonary bypass.