Introduction: Intimal thickening (IT) is an important remodeling for anatomical closure of the ductus arteirosus (DA). Although the immediate rise of oxygen tension at birth contracts DA smooth muscle, the role of oxygen in vascular remodeling remains unknown. Hypothesis: Raising oxygen tension promotes IT and anatomical DA closure. Methods: Tissues and vascular smooth muscle cells (SMCs) were obtained from the DA and aorta of rat fetuses on the 21st day of gestation. To examine the effect of raising oxygen tension, SMCs were cultured in a hypoxic chamber (1% O 2 , 5%CO 2 , pO 2 : 20 mmHg) for 3 days and then transferred to a normoxic chamber (21% O 2 , 5% CO 2 , pO 2 : 120 mmHg).Production of basic fibroblast growth factor (bFGF) and H 2 O 2 were measured by ELISA. The area of IT was evaluated by Elastica van Gieson stain. Immunohistochemical analysis was performed using human DA tissues from eight patients with various congenital heart diseases. Results: bFGF was highly expressed in the part of IT in human and rat neonatal DA. Oxygenation increased production of bFGF {1.6-fold (1h), 4.2-fold (6h), n=4-8, P <0.001}, H 2 O 2 {1.8-fold (10 min), n=6, P <0.01} and phosphorylation of ERK1/2 { 2.2-fold (15 min), n=5-9, P <0.001} in rat DA SMCs, but not in aortic SMCs. Inhibition of reactive oxygen species (ROS) by apocinin or rotenone, or ERK inhibitor U0126 attenuated oxygen-induced bFGF production. Oxygenation and recombinant bFGF promoted DA SMC migration (1.8-fold, n=6, P <0.001). Neutralizing antibody against bFGF, apocynin or rotenone attenuated oxygen-induced migration. In vivo study, intraperitoneal administration of anti-bFGF antibody, ROS inhibitor N -acetylcysteine or ERK1/2 inhibitor U0126 attenuated postnatal IT in full-term rat DA (0.8-fold, 0.8-fold, or 0.8-fold, respectively, n=4-10, P <0.01). Furthermore, administration of bFGF promoted IT in preterm rat DA (1.4-fold n=4, P <0.01). Co-administration of bFGF with a cyclooxygenase (COX) inhibitor, rather than a COX inhibitor alone, significantly enhanced IT and promoted closure of rat preterm DA. Conclusions: These results suggest that raising oxygen tension and subsequent induction of ROS induced bFGF secretion via ERK1/2, leading to postnatal anatomical losure of the DA.