Aim To determine that chronic intermittent hypobaric hypoxia （CIHH） could improve vascular calcification （VC） through blocked endoplasmic reticulum stress （ERS）.Methods He rats model of VC was induced by vitamin D3 plus nicotine （VDN）. The Ca²⁺ content of aorta and alkaline phosphatase （ALP） activity of aorta and plasma was detected. The protein expression level was measured by Western blot.Results Compared with the control group,Ca²⁺ content of aorta and alkaline phosphatase （ALP） activity of aorta and plasma was significantly increased in VDN rats （P<0.05）. In calcified vascular,the protein expression of contractile phenotype of vascular smooth muscle cell （VSMC）,calponin and SM22α,was down-regulated （P<0.05）,while that of osteoblast-like phenotype of VSMC,BMP2 and RUNX2 was up-regulated. CIHH could improve the all aboved issues （P<0.05）. Furthermore,CIHH could prevent the induction of protein level of ERS markers,GRP78,CHOP and active-caspase12 in calcified aorta （P<0.05）.Conclusions These results suggested that CIHH could ameliorate VC through inhibiting ERS,which might provide new strategy and target for prevention and therapy of VC.