Objective To investigate the effects of ulinastatin (UTI) on plasma cytokines following intermittent continuous ischemic reperfusion(IR, cumulative time >150min ) of both lower extremities.Methods Thirty patients, both low extremities bound with tourniquets during operation, were randomly divided into three groups: normal control group(Group NC), UTI pretreatment group 1(Group UP1) and group 2(Group UP2). The patients in Group UP1 were intravenously infused with UTI 6000 U/kg 15 min before the tourniquet application and the last tourniquet loosening, respectively. The patients in Group UP2 were intravenously infused with UTI 12 000 U/kg 15 min only before the last tourniquet loosening, UTI was diluted with 100 ml sodium chloride and infused intravenously within 10 minutes. The patients in Group NC were administered with the same volume sodium chloride. At the time, 20 min before tourniquet apptionhor(before IR); 30 min after last tourniquet lossening(30 min after IR); and 1 d, 3 d, 7 d after IR, the peripheral blood was sampled to measure plasma levels of C reactive protein(CRP), interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α).Results The levels of CRP, IL-6 and TNF-α in the three groups all rose significantly 30 min, 1 d and 3 d after IR compared with those before IR respectively(P<0.05). But the levels of the cytokines in Group UP1 and UP2 were significant lower than those in Group NC[CRP:1 d(11.15±2.32)、(10.48±2.08)mg/l vs NC(15.83±4.56)mg/l,3 d (4.29±1.89)、(3.89±1.34)mg/l vs NC(6.78±2.95)mg/l;TNF-α:1d(31.24±8.66)、(29.72 ±8.77)ng/l vs NC(44.802 ±11.70)ng/l,3 d (13.75±5.11)、(15.73±4.16)ng/l vs NC(20.787±8.05)ng/l;IL-6:1 d(160.80±46.95)、(179.72±35.77)ng/l vs NC(329.50±95.34)ng/l,3 d (45.32 ±16.53)、(53.35±17.62)ng/l vs NC(79.33±24.93)ng/l,P<0.05]. There were no significant differences between Group UP1 and Group NC in each time in terms of the cytokines(P>0.05). The inflammatory cytokines recovered to the same level 7 d after IR.Conclusions UTI pretreatement may relieve the system inflammatory reaction following both low extremities, prevent the increases of plasma cytokines after IR, thus may attenuate organ damage mediated by cytokines.