Aims Bone marrow (BM) progenitor cells may contribute to vascular remodelling. The present study aimed to investigate the contribution of BM-derived CXCR4+ (a CXC chemokine receptor) and PDGFRβ + (platelet-derived growth factor receptor) progenitor cells in hypoxia-induced muscularization of alveolar arterioles. Methods and results Accumulation of GFP+ (green fluorescent protein) cells was markedly increased in the pulmonary vasculature by the hypoxic (10 O2, 4 weeks) chimeric mice with transgenic GFP-tagged BM. After injection of BM-derived CXCR4+/PDGFR+ progenitor cells into C57BL/6J mice, followed by 6-week hypoxia, the cells were found to home to the alveolar arterioles and readily differentiated into smooth muscle cells (SMCs). Under the same hypoxic conditions, mice infused with myocardin lentiviral RNAi vector-transduced progenitor cells displayed lower myocardin expression in the muscularized alveolar arterioles, correlating with decreased pulmonary artery pressure and arteriole muscularization. In vitro experiments further confirmed that the differentiation of the progenitor cells into SMCs occurred under hypoxia (1 O2), and SMC differentiation could be suppressed when myocardin RNAi was administered. Conclusion Theses results suggest that myocardin may contribute to the differentiation of CXCR4+/PDGFR + progenitor cells into SMCs induced by hypoxia, which leads to the muscularization of alveolar arterioles. © 2010 The Author.