Objective To investigate the change of the neutrophil apoptosis and neutrophil respiratory burst in the patients and the effect of ulinastatin on the apoptosis of neutrophil and respiratory burst of neutrophil during cardiopulmonary bypass (CPB). Methods Sixty-two patients undergoing valve replacement with CPB were randomly divided into two groups: ulinastatin group (U group, 31 cases) and control group (C group, 31 cases). In U group patients received ulinastatin after induction of anesthesia. In C group patients received equal volume of normal saline, instead of ulinastatin. Arterial blood was obtained before operation (T1), 30 min after the start of CPB (T2), 30 min after the termination of CPB (T3). The apoptosis of neutrophil and respiratory burst of neutrophil were measured by flow cytometer. The level of superoxide dismutase (SOD) and malondialdehyde (MDA) were measured by kit. Results In C group, compared with T1 [(66.57±5.93)%], the rate of the apoptosis of neutrophil was significantly decreased at T2[(55.37±3.51)%] and T3 [(48.92±4.21)%] (P<0.05). And in U group, compared with T1 [(73.57±7.94)%], the rate of the apoptosis of neutrophil was significantly decreased at T2 [(68.34±4.92)% ] and T3 [(62.13±4.76)%] (P<0.05), And it reached to the minimum at T3. The rate of the neutrephil apeptosis was significantly lower in C group than that in U group (P<0.05). The respiratory burst of neutrophil increased significantly after the start of CPB and reached to the peak at T3[C group (1422.50±89.75) MCF,U group (1156.52±93.20) MCF]. The respiratory burst of neutrophil in U group was significandy lower than that in C group at T2 and T3 (P<0.05). The vitality of SOD decreased significantly after the start of operation in the two groups (P<0.05). The level of MDA increased significantly after the start of operation in the two groups, and reached to the peak at T3. The vitality of SOD in C group was significantly lower than that in U group at T3 (P<0.05). The level of MDA in C group was significantly higher than that in U group at T3 (P<0.05). Conclusions The rate of neutrophil apoptosis decreased and the respiratory burst of neutrophil increased during CPB. By improving the apoptosis of neutrophil and reducing the respiratory burst of neutrophil, ulinastatin can inhibit inflammatory reaction during CPB. Meanwhile, ulinastatin can improve the vitality of SOD and reduce the level of MDA. In conclusion, ulinastatin has a significant protective effect during CPB.