Abstract： Objective To observe the effects of three dosages of nebulized unfractioned heparin (UFH) on alveolar coagulation,inflammation and lung histology in endotoxin-induced acute lung injury rat model,and investigate the appropriated dose of local UFH in managing intrapulmonary coagulopathy.Methods Twenty-nine male Wistar rats were divided into control (n=5) and UFH group (n=24) in table of random number,which were duplicated to be endotoxin-induced ALI rat model with lipopolysaccharide (LPS) injecting by intravenous route.The UFH group was divided into three subgroups,which were administered once with 6,12 and 18 U/g aerosolized UFH in 10 ml at 2 hours after challenge,respectively,while the control group was simply nebulized with normal saline.All rats were sacrificed at 6 hours after intravenous administration of LPS,bronchoalveolar lavage was performed,and the fluid was collected.Enzyme-linked immune sorbent assay (ELISA) was used to measure the level of thrombin-antithrombin complex (TATc),tumor necrosis factor-α (TNF-α) in bronchoalveolar lavage fluid (BALF),and lung wet/dry (W/D) weight ratio,histology score were recorded.Results At 6 hours after LPS-induced lung injury,the levels of TATc (μg/L) and TNF-α (ng/L),lung W/D weight ratio and histology score in 6 U/g and 12 U/g group were all lower than those of control group significantly (TATc:0.959 ± 0.681,1.165 ± 0.854 vs.2.141 ± 0.791,TNF-α:4.449 ± 5.054,9.096 ±4.099 vs.18.184 ± 3.869,W/D weight ratio:7.018 ± 1.137,7.367 ± 0.349 vs.8.472 ± 0.614,histology score:16.0 ±1.0,16.5 ± 1.5 vs.19.6 ± 0.4,P＜0.05 or P＜0.01 ).There was no significant difference in the comparisons between the subgroups of UFH in TATc level in BALF and lung histology score.For the TNF-α level in BALF,18 U/g group evidently exceeded that of 6 U/g group ( 15.503 ± 8.753 vs.4.449 ± 5.054,P＜0.01 ),and lung W/D weight ratio in 18 U/g group was also significantly higher comparing to 6 U/g (8.850 ± 1.157 vs.7.018 ± 1.137,P＜0.05 ) and 12 U/g group ( 8.850 ± 1.157 vs.7.367 ± 0.349,P＜0.05 ).Conclusion It was appropriate for the dose of nebulized UFH to be administered no more than 12 U/g in ALI treatment,which was enough to inhibit alveolar coagulant cascade,decrease early inflammatory response and alleviate lung tissue injury.