Primary pulmonary hypertension (PPH) is still a refractory disease, and patients deteriorate despite any treatment. We hypothesized that neovascularization in the lung could increase the volume of the vascular bed in the pulmonary circulation and thus reduce the development of pulmonary hypertension (PH). Endothelial progenitor cells (EPCs) might be a potential cell source for neovascularization. We examined the effects of EPC transplantation into the lungs of dogs with dehydromonocrotaline-induced PH. The lung parenchyma of PH model dogs was injected with ex vivo-expanded, autologous EPCs originated from peripheral blood (experiments, n=4) or culture medium (control, n=3), using a bronchoscope. EPC transplantation gave significant improvements in mean pulmonary artery pressure, cardiac output, and pulmonary vascular resistance. Histological evaluation revealed both improvement in the medial thickness of the small pulmonary artery and neovascularization of the lung tissue. These results indicate that EPC transplantation into the lung is effective at preventing the progression of dehydromonocrotaline-induced PH in dogs, and suggest a new therapeutic option for PPH.