Objective To investigate the effect of ulinastatin (uli), a drug that can regulate the systemic inflammation response, on the preventive analgesia. Methods 80 patients aged 65-80, scheduled for selective orthopedic surgery on lower extremities were randomly divided into four groups of 20 each. After epidural catheterization, all patients were induced and maintained under total intravenous anesthesia (TIVA). Every patient used patients-controlled epidural analgesia (PCEA) to relief the postoperative pain. Patients in group A received uli 2×105IU after induction and before skin incision, then were administered continuously at rate of 2×105IU/h until the end of the operation; Patients in group B were given 1%ropivacaine (5-10)ml in the epidural space 15-20min before surgery and additional (5-10)ml every 45-60min during the operation; Patients in group C combined the protocols of group A and group B. Group D was the control group. Every patient’s sex, age, weight, height, ASA classification, operation style, operation duration, blood loss, the first time of pressing the PCEA, and the frequency of effective or actual press on the PCEA were recorded. VAS was obtained at rest and with movement preoperatively and at 1, 2, 3, 7 days after surgery. Blood samples were taken preoperatively and at 1, 3, 7 days after surgery for determination of IL-6, IL-10. Results Sex, age, weight, height, ASA classification, operation style, operation duration, blood loss and the level of IL-6, IL-10 preoperatively were similar among the four groups（P＞0.05）. After surgery, the concentration of IL-6 decreased in group A and C, and increased in group B and D, while that of IL-10 increased in group A and C, decreased in group D, and had little change in group B（P＜0.05）. Before surgery, VAS, whether with movement or not, showed no significant difference among groups（P＞0.05）. At rest, all groups reached satisfactory analgesia (i.e. VAS＜3), but the score of group D was higher than that of other groups at any days（P＜0.05）; while when with movement, all reached satisfactory analgesia except group D. VAS decreased at 1day postoperatively in group C, and at the 7 days it still failed to decreased below 3 in group D. Conclusion The use of uli to regulate the systemic inflammation response during the operation can relief postoperative pain to some extent，but its efficiency can not be compared with epidural anesthesia which has been confirmed to show a “preemptive analgesia” effect in the previous studies, while combining these two methods may lead a better outcome.