Objective To investigate the protective effect of adiponectin (APN) on lung injury in LPS-induced septic rats and whether the protective effect is mediated by heme oxygenase-1(HO-1). Methods 80 Wistar male rats were randomly divided into 4 groups: control group(C group), LPS group, adiponectin treatment group (APN group) and zinc protoporphyrin IX (ZnPP IX) treatment group (Zn group).At 6 h after intraperitoneal injection of lipopolysaccharide (LPS), the serum levels of tumor necrosis factor (TNF)-α and interlukin (IL-6) were detected by ELISA. The serum level of nitric oxide (NO), malonodialdehyde (MDA) content and myeloperoxidase (MPO) activity in lung tissue were detected by spectrophptometry. Lung HO-1, inducible nitric oxide synthase (iNOS) mRNA were detected with real time pohymerase chain reaction(RT-PCR). The mortality rate was calculated 7days after operation and the survival curves were drawn. Results The serum levels of TNF-α[ (321.3±11.2), (132.5±10.2), (311.7±12.4) vs (52.1±1.4)] ng/L, IL-6 [(2 229.26±210.25), (1 134.14±11.24), (2 028.27±167.04) vs (55.38±0.23) ] ng/L and NO[ (103±10), (79±8), (97±9) vs (48±3)] μmol/L in LPS, APN, Zn groups were higher than those in C group (P<0.05). The MDA concentration [(16.209±0.151), (5.943±0.310), (13.238±0.326) vs (3.081±0.017) ] nmol/mg and MPO activity [(12.42±0.46), (6.77±0.14), (10.45±0.21) vs (2.74±0.06)] U/g in lung homogenate in LPS group were higher than those in C group (P<0.05). The survival rate of rats in LPS, APN, Zn groups were lower than that of C group (20% vs 100%; 70% vs 100%; 30% vs 100%, P<0.05). The serum levels of TNF-α[ (311.7±12.4) vs (132.5±10.2)] ng/L, IL-6 [(1 134.14±107.13) vs (2 229.26±210.25) ] ng/L and NO[ (79±8) vs (103±10)] μmol/L in APN group were decreased as compared with LPS group (P<0.05). The MDA concentration [(5.943±0.310) vs (16.209±0.151)] nmol/mg and MPO activity[(6.77±0.14) vs (12.42±0.46)] U/g in lung homogenate and the lung iNOS mRNA [(1.42±0.15) vs (2.01±0.10)] in APN group were decreased as compared with LPS group (P<0.05). The lung HO-1 mRNA in APN group was higher than that in LPS group[ (8.73±0.24) vs (1.54±0.03) (P<0.05)]. The survival rate of rats in APN group was lower than that of LPS group (70% vs 20%, P<0.05). The serum levels of TNF-α[ (311.7±12.4) vs (132.5±10.2)] ng/L, IL-6[(2 028.27±167.04) vs (1 134.14±107.13) ] ng/L and NO [(97±9) vs (79±8)] μmol/Lin Zn group were increased as compared with APN group (P<0.05). The MDA concentration [(13.238±0.326) vs (5.943±0.310)] nmol/mg and MPO activity [(10.45±0.21) vs (6.77±0.14)] U/g in lung homogenate and the lung iNOS mRNA [(2.06±0.23) vs (1.42±0.15)] in Zn group were raised as compared with APN group (P<0.05). The lung HO-1 mRNA [(2.66±0.14) vs (8.73±0.24)] in group Zn was decreased as compared with APN group (P<0.05). The survival rate of rats in Zn group was lower than that of APN group (30% vs 70%, P<0.05). Conclusions HO-1 may mediate the protective effect of adiponectin on lung injury in LPS-induced septic rats.