Objective To investigate the nuclear factor-erythroid 2-related factor (Nrf-2),and hemeoxidase 1 (HO-1) expression in acute lung injury induced by paraquatpoisoning in rats and explore the mechanism of lipoic acid acting on protection of lung from paraquatpoisoning.Methods Seventy-two adult healthy male Sprague Dawley (SD) rats were randomly divided into three groups with different treatments designated ascontrol group (control group,n =12),paraquat group (PQ group,n =30) and paraquat + lipoic acid group (LA group,n =30).PQ group and LA group were randomly divided into five subgroups (n =6 in each) according to 6 h,12 h,24 h,48 h and 72 h after modeling and treatment.The rats in PQ group and PQ + LA group were treated with intra-peritoneal injection (ip) of PQ (25 mg/kg),while the rats in control group were treated with the equal volume of saline instead.Half an hours after intra-peritoneal injection of PQ,lipoic acid (100 mg/kg) was injected into caudal vein of rats once a day until they were sacrificed.The body weight was measured everyday.The rats of each group were sacrificed at the given intervals,and lungtissues were harvested to measurelung coefficient of rats.The same part of left lung of rats in each group was taken for HE staining and immunohistochemistry in order to detect the expressions of Nrf2 and HO-1.The right lung of rats in each group was taken for the detection of GSH-Px and SOD activity.All data were analyzed by using the One-way analysis of variance (ANOVA) and SNK-q test.Results The body weight reduction in LA group (191.02 ± 0.82) g,(183.37 ± 7.74) g was significantly less than that in PQ group (183.85 ± 2.07) g,(173.13 ± 4.34) g at 48 h and 72 h after PQ poisoning,respectively (P < 0.01,P < 0.05).The lung coefficient in LA group (6.83 ± 0.48) mg/g,(7.61 ±0.28) mg/g,(8.29 ±0.36) mg/g was less compared with PQ group (7.39 ±0.53) mg/g,(8.48±0.23) mg/g,(9.06±0.10) mg/g at 24 h,48 h,and 72 h,respectively (P<0.01,P< 0.05).The immunohistochemical expressions of Nrf-2 in LA group (3.99 ±0.50),(3.51 ±0.12) were higher than those in PQ group (1.33 ±0.22),(1.62 ±0.41) at 48 h and 72 h.The immunohistochemical expression of HO-1 in LA group (1.76 ±0.17) was higher than that in PQ group (1.31 ±0.15) at 72 h.The levels of GSH-Px activity in LA group were significantly higher in comparison with PQ group at 24h,48h,and 72h (P <0.01,P <0.05).The levels of SOD activity in the LA group were significantly higher in comparison with PQ group at 6 h,12 h,24 h,48 h,and 72 h after PQ administration (P < 0.01).Conclusions Nrf2-ARE (antioxidant response element) signaling pathway is involved in the pathogenesis of acute lung injury induced by paraquatpoisoning,and lipoic acid may protect acute lung injury in rats induced by paraquatpoisoning through Nrf2-ARE signaling pathway.