Objectives To investigate the role of HIF-1α and NF-κB in intermittent hypoxia (IH) induced atherosclerosis in rabbits. Methods New-Zealand White rabbits were exposed to IH for 12 weeks (intermittent hypoxia of 21% O2 for 30 s and 8% O2 for 30 s, cyclically repeated for 8 h/day). We randomly assigned 48 male rabbits to groups of normoxia (RA) or IH. The rabbits in the RA group were continuously exposed to room air. After intervention of 4, 8, and 12 weeks, serum and aortic arch tissues were subjected to Elisa and immunohistochemical staining analyses respectively. The formation of atherosclerosis in the aortic arch was observed by HE. Results The formation of atherosclerosis in aortic tissue was observed by HE staining after IH. Compared with the RA rats, the level of HIF-1α and NF-κB in the serum of IH rats started to increase 4, 8, and 12 weeks after the beginning of the experiment (p 0.05). NF-κB protein expression was significantly increased after IH (p Conclusions IH may, through increased HIF-1α and NF-κB in rabbits, lead to lipid deposition, which leads to the formation of atherosclerosis and the occurrence of cardiovascular and cerebrovascular diseases.