Objective: The main aim of this study is to investigate the beneficial effects of mild chronic intermittent cold(CIC)exposure on the effects of high-fat diet feeding(HFD) on liver oxidative stress in SD rats. Methods: Mild CIC has been widely used to establish the animal model of cold adaptation. HFD(45% of fat) and CIC(4℃, 6 hours/day) were given concurrently to the rats for 4 weeks. The rectal temperature, body weight, liver weight, the levels of ATP and reactive oxygen species(ROS) in liver are measured after 4 weeks of rats exposed to mild CIC and/or HFD. The protein level of cold inducible RNA binding protein(Cirbp) and thioredoxin(TRX) are detected by western blotting. Results: Compared with the control group, the body weight of the high fat diet group increases significantly, the ROS level increases significantly, and the level of ATP has no significant effect; the rectal temperature of rats decreases significantly after 1 d and 1 w of CIC exposure, while the rectal temperature has no significant difference after CIC exposure of 2 w, 3 w and 4 w; there's no significant difference in the level of ROS, but the ATP level and the expression of Cirbp and TRX are increased significantly. Compared with HFD group under normal temperature, the body weight decreases significantly after CIC exposure 4 w, the level of ROS had no significant difference, while ATP level increased significantly; the expression of Cirbp and TRX increased significantly. These results suggest that cold adaptation enhances the antioxidant level in the liver of HFD rats, probably due to the increased expression of Cirbp after cold acclimation, and then increases the expression of the antioxidant protein TRX, thus cleaning ROS. Conclusion: Cold adaptation induced by CIC exposure protects the liver against oxidative stress induced by HFD. [ABSTRACT FROM AUTHOR]