〔Abstract〕 Objective To investigate the role of endoplasmic reticulum stress in hepatic insulin resistance induced by intermittent hypoxia in rats. Methods Twenty-four SD rats were randomly divided into control group(NC group) and intermittent hypoxia group(CIH group). The NC group was placed in a normoxia environment for 12 weeks, and the CIH group was given intermittent hypoxia for 8 weeks, and then returned to normoxia until the 12 th week. In both groups, fasting blood glucose(FBG), fasting insulin(FINS), and liver inositol-requiring enzyme-1α(IRE1α), X-box binding protein 1 s(XBP1 s), forkhead box transcription factor O1(FoxO1), activating transcription factor-6( ATF6),c AMP-response element binding protein( CREB),CREB-regulated transcription coactivator-2( CRTC2),double-stranded RNA-dependent protein kinase-like ER kinase( PERK),eukaryotic initiation factor 2α( e IF2α),protein kinase B( AKT),phosphoenolpyruvate carboxykinase( PEPCK),glucose-6-phosphatase( G6Pase) mRNA were measured at baseline,week 8,and week 12. Results There was no significant difference in each observation index between the two groups at baseline; at 8 weeks,the levels of FBG,FINS and the mRNA levels of IRE1α,XBP1s,ATF6,PERK,e IF2α,PEPCK and G6Pase in the CIH group were higher than those in the NC group( P<0. 05),while the mRNA levels of CREB,CRTC2 and AKT were lower than those in the NC group( P<0. 05); at 12 weeks,there was no significant difference in each observation index between the two groups. Pearson correlation analysis showed( 8th week of intermittent hypoxia group) : homeostasis model assessment-insulin resistance( HOMA-IR) was positively correlated with Fox O1,CREB,CRTC2 and PERK,e IF2αmRNA levels( r = 0. 172,0. 595,0. 183,0. 702,0. 608; P<0. 05) while it was negatively correlated with IRE1α,XBP1s,ATF6,AKT mRNA levels( r =-0. 422,-0. 327,-0. 309,-0. 399; P<0. 05). Conclusion Intermittent hypoxia can lead to insulin resistance,and endoplasmic reticulum stress may mediate this effect.