Objective To investigate the effect of hypoxia inducible factor-1α(HIF-1α) inhibitor(YC-1) pretreatment on Toll-like receptor 4(TLR4) mRNA expression in the lung following acute lung injury(ALI) induced by intestinal ischemia-reperfusion(I／R) injury in mice． Methods Thirty-six healthy male C57BL/6 mice weighing 20-24 g were randomly divided into 3 groups(n=12 each)：Sham operation group(group S)；intestinal I／R group(group I/R)；YC-1 administration before ischemia group(groupYC-1).YC-1 1mg/kg was injected intraperitoneal at 10 min before ischemia in group YC-1.Intestinal I／R injury was induced by clamping the superior mesenteric artery for 45min and the mice were sacrificed at 6 h of reperfusion.The lungs were immediately moved for microscopic examination,determination of W/D lung weight radio and MPO activity, levels of TNF-α and L-1β,HIF-1α and TLR4 mRNA expression in the lung tissue(by RT-PCR)．Results Microscopic examination showed that there were collapse or consolidation alveoli,edema and infiltration of neutrophils in the lung parenchyma in I/R group.Intestinal ischemia reperfusion significantly increased W／D lung weight ratio,MPO activity, levels of TNF-α and L-1β,HIF-1α and TLR4 mRNA in the lung tissu．The lung injury was significantly ameliorated in group YC-1 as compared to group I/R.Pretreatment with YC-1 significantly inhibited intestinal ischemia reperfusion-induced increase in W／D lung weight ratio,MPO activity,levels of TNF-α and L-1β,HIF-1α and TLR4 mRNA in the lung tissue. Conclusion YC-1 pretreatment before ischemia can reduce ALI induced by intestinal ischemia reperfusion through down-regulation of TLR4 mRNA expression and decreasing levels of TNF-α and IL-1β in the lung．