Objective:To investigate the effects of ulinastatin(UTI) on systemic and cerebral inflammatory response and on brain protection during cardiopulmonary bypass(CPB). Methods:Twenty-four patients,undergoing elective cardiac valve replacement were randomly divided into 2 groups:ulinastatin group(Group U,n = 12) and control group(Group C,n = 12). In group U,UTI(1×104 U/kg) was infused intravenously after the induction of anesthesia and during CPB, respectively. Each infusion time was about 1 h. In Group C,normal saline was given instead of UTI. Blood samples were taken simultaneously from artery and jugular bulb after induction of anesthesia(T1),0.5 h after CPB beginning(T2),1 h(T3),4 h(T4) and 20 h(T5) after CPB termination for determination of TNFα,IL-6 and S100B. S100B samples were taken only from jugular bulb. The jugular bulb-arterial gradients of these cytokines(△TNFα and △IL-6) were calculated. Results:The concentration of TNF-α,IL-6,△TNF-αand △IL-6 elevated dramatically at T2,T3,T4,T5 in both groups(P < 0.01 or P < 0.05). TNF-α,IL-6,△TNF-α and △IL-6 at T2,T3,T4,T5 in group C were higher than that at the corresponding time point in group U. Compared with T1 point,the level of S100B increased markedly 30 min after CPB(T2)(P < 0.01),reached peak level at T3 point and began to decrease at T4 point in both groups. The levels of S100B at T2,T3,T4,T5 in Group U were lower compared with group C at the corresponding time point. Conclusion:Systemic and cerebral inflammatory response during CPB could be alleviated by ulinastatin, and Jugular bulb blood levels of S100B Protein decreased by ulinastatin. Ulinastatin had protective effect on the brain injury during CPB.