Chronic intermittent hypoxia reduces the bodyweight gain induced by HFD and improves insulin resistance. Experimental mice were exposed to ambient oxygen (normoxia) or 10% oxygen for one hour every day. (A) Scheme of grouping (8 mice per group): (1) chow diet and normoxia, (2) chow diet exposed to 10% oxygen, (3) HFD and normoxia, (4) HFD and 10% oxygen simultaneously, (5) HFD for 4 weeks and then 10% oxygen applied. (B) Body weight was measured every two weeks. Statistical analysis was performed by two-way ANOVA (mean ± SEM, n = 8). *** p < 0.005. (C) The value of bodyweight gain was obtained by subtracting bodyweight at the starting point from the endpoint (mean ± SEM). * p < 0.05. (D) Food intake (g/day/mouse) was recorded for one week and averages were presented. * p < 0.05, ns means not significant. (E) Fasting blood glucose levels wee measured. Significance was tested by Student’s t-test (mean ± SEM), *** p < 0.005. (F,G) Glucose tolerance test (GTT) and insulin tolerance test (ITT) were carried out. AUC for F: HFD, 1781; HFD 4 w + 10% O2, 1590; Simultaneous HFD + 10% O2, 1517; Chow, 1136. AUC for G: AUC: HFD, 59.05; HFD 4 w + 10% O2, 54.77; Simultaneous HFD + 10% O2, 53.85; Chow, 39.82. Significance was tested using two-way ANOVA (mean ± SEM). p < 0.05 (Group 3 vs. Group 4 and Group 3 vs. Group 5, respectively).