On the Co-culture model of pulmonary arterial endothelial cells (PECs) and smooth muscle cells (PSMCs), we studied the effects of hypoxia on the release of endothelin in cultured PECs and whether or not these effects could trigger the proliferation in PSMCs. Increase of the transcription of ET gene in cultured pulmonary arterial endothelial cells was shown when endothelial cells were exposed to hypoxia for 24h (95% N2 + 5% CO2, PO2 40-45mmHg in media), was showed to increase the transcription of ET gene in cultured pulmonary arterial endothelial cells by using situ hybridization method. The secretion of ET-1 from those cells into media by ET-1 radioimmunologic detection while 3HTdr incorporation in cultured PMCs was higher compared with normoxia, and administration of ETAb significantly reduced the increase of the incorporation in those compared with hypoxia alone. These results showed that exposure to hypoxia can promote ET-1 gene expression in PECs as well as release of ET from those cells, which of ET can stimulate DNA synthesis in cultured PMCs. It is suggested that enhanced ET release from PECs under hypoxia could stimulate PSMCs' proliferation which may induce pulmonary vessel remodeling--which may involve in the development of hypoxic pulmonary hypertension.