Objective: To determine the role of hemoglobin(HB) -induced heme oxygenase- 1 ( HO- 1 ) in injured lungscaused by limb ischemia-reperfusion (I/R) in rats.Methods: A rat model of ischemia in the hind limbswas made by clamping the infrarenal aorta with amicrovascular clip, and lung injury occurred afterreperfusion. To induce the expression of HO-1 in the lungs,Hb was administrated intraperitoneally at 16 hours beforereperfusion. North blotting and West blotting wereused to detect the expression of HO-1 in the lungs, and thecarboxyhemoglobin (COHb) level in arterial blood wasassayed. The effect of hemoglobin (Hb) on the injuredlungs after limb I/R was determined by measuring thechanges of lung histology, polymorphonuclear (PMN)count, malondialdehyde (MDA) content and wet-to-dryweight ratio (W/D). Zinc protoporphyrin (ZnPP), aninhibitor of HO, was used to determine whether HO-1 wasinduced by Hb after lung injury.Results: Hb led to a significant increase in HO-1mRNA and protein expression in the lungs, accompanied bythe increase of COHb level in arterial blood. Comparedwith the sham controls, the lung PMN count, MDA contentand W/D significantly increased at 4 hours after limb I/R,which reversed by the pretreatment with Hb at 16 hoursbefore reperfusion. ZnPP blocked this protective role of Hbin the injured lungs.Conclusions: Hb can induce the lung HO-1expression, which plays an important role in the defenseagainst I/R-induced lung injury in rats.