Aim To investigate the effects of perinatal hypoxia on carotid artery endothelium-dependent relaxations of 6 week old rabbits and its molecular mechanism.Methods Ten pregnant New Zealand White rabbits were randomly divided into two groups: normoxic control group (21% O₂, n5) and perinatal hypoxia group (12% O₂, n5) during day 10～29 of pregnancy. Pregnant rabbits had spontaneous deliveries, and only one male offspring from each litter was selected randomly and breast-fed for six weeks. Carotid arteries were obtained from 6 week old rabbits, endothelium-dependent relaxation (EDR) and expression of endothelial nitric oxide synthase (eNOS) and heat shock protein 90 (HSP90) of carotid arteries were examined.Results Perinatal hypoxia significantly impaired carotid artery EDR in 6 week old rabbits (P<0.05). Perinatal hypoxia significantly decreased carotid artery HSP90 expression (P<0.05) and eNOS activities (P<0.05) in 6 week old rabbits.Conclusions Perinatal hypoxia can induce functional impairment in vascular endothelium from 6 week old rabbits. The molecular mechanism involved is that perinatal hypoxia decrease HSP90 expression and eNOS activities of rabbit artery.