Hepatocyte growth factor (HGF) has recently been noted to function as a pulmotrophic factor for lung regeneration. The present study was conducted to determine if HGF would be induced in a rat model of pulmonary ischemia-reperfusion (IR) injury, which was established by occlusion of the left lung, and to examine the significance of HGF in subsequent lung repair. The sham-operated rats underwent simple thoracotomy in which the lung was not clamped. We measured the plasma and the tissue levels of HGF by enzyme-linked immunosorbent assays, and the expression of HGF mRNA by Northern blotting. The plasma HGF level was markedly elevated after pulmonary ischemia and reached the peak value on the third postoperative day, being 5-fold higher than that of the sham-operated rats. HGF mRNA expression and the tissue HGF levels were augmented twofold in the ischemic reperfused lung. Immunohistochemical analysis revealed that the infiltrating alveolar macrophages were intensely stained for HGF. DNA synthesis of alveolar epithelial cells, as identified by proliferating cell nuclear antigen (PCNA) staining, was 3-fold higher in the reperfused lung than in the sham-operated lung. Notably, HGF-neutralizing treatment with an anti-HGF antibody reduced DNA synthesis of alveolar epithelial cells in the reperfused lung and aggravated lung injury. This study shows that HGF was induced in the ischemic reperfused lung and may play an important role in regeneration of an injured lung after pulmonary IR.