Abstract： Objective To study and compare the protective effects of pmtease inhibitor and corticosteroid on endotoxin-indueed acute lung injury in order to guide the choice of appropriate drugs. Method Thirty-two New Zealand rabbits were randomly divided(random number) into four groups with 8 rabbits in each, namely normal controls(C) ; lipopolysaecharide(LPS) group(L) ; ulinastatin(UTI) group(U) and dexamcthasone(DEX) group (D) .Except group C, all rabbits were injected with a dose of LPS 600 μg/kg iv. Meanwhile the rabbits in group U,group D received UTI(100 000 μ/kg), DEX(5 mg/kg), respectively. The specimens were collected 4 hours later for detecting the levels of TNF-α and NO in serum, and blood gas analysis, histological manifestations, the lung wet/dry weight ratio, lung tissue MPO and SOD activity, lung tissue MDA. Data were analyzed by ANOVA (SNK- q test), and P < 0.05 was considered as significantly different. Results Compared with group C, the lungs of the rabbits in group L had inflammatory granulocyte infdtration, diffused alveolar septum thickening and hemorrhagic spots were observed in pathological examinations. The histological changes of group U and group D were much lessened than those in group L. As groups U and D were compared with group L, there were significant differences inmany biomarkers including lung wet/dry weight ratio[(5.02±0.11),(4.93±0.13) vs.(5.37 ±0.29)],lung tissue MPO activity[(0.51 ± 0.05),(0.54±0.07) vs.(0.82 ± 0.09)] and MDA[(0.82 ±0.05),(0.81 ±0.04) vs.(0.96±0.05)], NO[(296.2± 11.7),(291.7 ± 15.8) vs.(351.8±19.6)] and TNF-α[group D(2.021 ± 0.122) vs. group L(4.999 ± 0.139)],lung tissue SOD activity[(120.3 ± 6.1),(122.6±3.5) vs.(105.1 ± 8.5)] and blood gas analysis[pH(7.30±0.23),(7.30±0.17) vs.(7.22±0.45) and PaO_2( 101.9 ± 6.8).( 102.5 ± 4.7) vs.(80.3 ± 3.3)] ; but there were no differences of above mentioned biomarkers between group U and D( P > 0.05). And there were no significant differences in PaCO_2 betweeu group U and D and group L[(37.0 ± 3.3),(37.6 ± 3.0) vs.(34.8 ± 2.3)]( P > 0.05). Conclusions The protective effects of ulinastatin on endotoxin-induced acute lung injury is comparable to those of dexamethasone, thus the former may be a clinical substitute for the latter with less side effects.