Objective To determine the intervention effects of adiponectin (Ad) on rat kidney injury induced by chronic intermittent hypoxia (CIH), and investigate the underlying mechanisms. Methods Sixty adult Wistar rats were randomly divided into 4 groups:normal control (NC group), normal control plus Ad supplement (NC+Ad group), CIH, and CIH plus Ad supplement (CIH+Ad group) groups. The rats in both CIH and CIH+Ad groups were submitted to a CIH environment for 4 months, while the rats in NC and NC+Ad groups were housed with the normal air for 4 months. In addition, the rats in NC+Ad and CIH+Ad groups were treated with an intravenous injection of Ad at a dosage of 10 μg per injection, twice a week, for 4 successive months. Fluorescence microscopy was used to observe the levels of reactive oxygen species (ROS). TUNEL staining was employed to detect the apoptosis of renal cells. Western blotting was adopted to measure the expression levels of GRP78, CHOP, IRE1, PERK and pro-ATF6 in renal tissues of rats in each group to indicate the stress of endoplasmic reticulum in rats. SPSS statistics 17.0 was used to analyze the data. The measurement data were expressed as mean±standard deviation ([AKx-D]±s), and student’s t test was used for the comparison between the groups. Results In the end of 4 months’ treatment, no significant differences were found in all the parameters between the NC and NC+Ad groups (all P>0.05). Compared with the NC and NC+Ad groups, our findings were as follows:(1) ROS levels were significantly higher in the CIH group, while the levels in the CIH+Ad group was though lower than those in the CIH group, but higher than those in the NC and NC+Ad groups (all P<0.05); (2) the percentage of apoptotic renal cells and protein levels of caspase-12 and caspase-3 were all significantly higher in the CIH group, while in the CIH+Ad group, they were lower than in the CIH group, but still higher than in the NC and NC+Ad groups (all P<0.05); (3) the protein levels of GRP78, CHOP, IRE1 and PERK in the renal tissues were all significantly higher in the CIH group, while in CIH+Ad group, the levels were lower than in the CIH group, but higher than in the NC and NC+Ad groups (all P<0.05); the protein level of pro-ATF6 in the renal tissues was lower in the CIH group, while in the CIH+Ad group, the level was higher than in the CIH group, but lower than in the NC and NC+Ad groups (all P<0.05). Conclusion CIH induces kidney injury through activation of ROS and ERS-associated cellular apoptotic pathway, while exogenous Ad supplement protects the renal cells by inhibiting ROS and then ERS.