Objective To investigate the existence of pulmonary vascular remodeling after left pneumonectomy in rats and the role of hypoxia inducible factor-lα (HIF-1α) and vascular endothelial growth factor (VEGF) in pulmonary vascular remodeling. Methods Twenty-four healthy male Sprague-Dawley rats were randomly divided into experimental and control groups, 12 in each group. The rat models of pulmonary vascular remodeling were created by open-chest left pneumonectomy. After 12 weeks of feeding, the mean pulmonary artery pressure (mPAP) and partial pressure of arterial oxygen (PaO₂) of each rat were measured. The ultrastructure of small arteries in the lung specimens were examined by electron microscopy. Muscularized degree of three kinds of small pulmonary vessels (muscularized artery MA, partially muscularized artery PMA, and non-muscularized artery NMA) were observed by light microscopy, and the percentage of each kind of pulmonary arteries (MA%, PMA%, NMA%) were calculated. Arterial external diameter, media thickness of vessel (MTV), total vascular area, media area of vessel (MAV), MTV% and MAV% were calculated as indicators of pulmonary vascular remodeling. The expressions of HIF-1α and VEGF in artery were detected by immunohistochemistry. Results The values of mPAP, MA%, PMA%, MTV, MAV, MTV% and MAV% in the experimental group were significantly higher than those in the control group (P<0.01), but the value of PaO₂ and NMA% were significantly lower than those in the control group (P<0.01). The IOD value of HIF-1α and VEGF expressed in the pulmonary arterial wall of the experimental group were 26.47±4.16 and 42.04±3.79, respectively, significantly higher than those in the control group (6.12±2.14 and 11.53±2.29, P<0.01). Linear correlation analysis showed that the expression of HIF-1α and VEGF was positively correlated with MTV% and MAV%, negatively correlated with PaO₂, and the HIF-1α expression was positively correlated with VEGF expression. Conclusions A rat model of pulmonary vascular remodeling can be successfully established by left pneumonectomy. Hypoxia is a key factor in the development of pulmonary vascular remodeling, HIF-1α and VEGF may play an important role in its pathogenesis.