Hypoxia inducible transcription factor (HIF)-1α plays an important role in the development of hypoxic pulmonary hypertension, but little is known about HIF-2α and HIF-3α with respect to transcriptional regulation by hypoxia. To examine the expression pattes of all HIF-α subunits (HIF-1α, HIF-2α and HIF-3α) in pulmonary arteries of rats undergoing systemic hypoxia, five groups of healthy male Wistar rats were exposed to normoxia (N) and hypoxia for 3 (H3), 7 (H7), 14 (H14) and 21 (H21) d respectively. Mean pulmonary arterial pressure (mPAP), vessel morphometry and right ventricular hypertrophy index were measured. Lungs were inflation fixed for immunohistochemistry and in situ hybridization, and homogenized for Weste blot. mPAP increased significantly after 7 d of hypoxia [(18.4±0.4) vs. (14.4±0.4) mmHg, H7 vs.N], reached its peak after 14 d of hypoxia, then remained stable. Pulmonary artery remodeling and right ventricular hypertrophy developed significantly after 14 d of hypoxia. During normoxia, HIF-1 α and HIF-3α staining were slightly positive regarding mRNA levels. A substantial alteration of HIF-1 α and HIF-3α staining occurred in pulmonary arteries after 14 d and 7 d of hypoxia, respectively, but HIF-2α stainin g showed an inversed trend after 14 d of hypoxia. Protein levels of all HIF-α subunits except HIF-3α showed a marked increase corresponding to the duration of hypoxia, which was obtained by Weste blot. Our study found that HIF-1 α, HIF-2α and HIF-3α may not only confer different target genes, but also play key pathogenetic roles in hypoxic-induced pulmonary hypertension.