Objective To investigate the change of aquaporin 2 (AQP2) mRNA and protein levels in renal collecting duct of SD rats after hypoxin caused by rising of the altitude to 4600 m. Methods Forty male SD rats were randomly divided into 4 groups (24 h, 48 h, 72 h and 1 week group), and 10 rats in Xining city were used as control group. All the 40 SD rats were transported to Kekexili Natural Reservation areas (4600 m) in Qinghai province. Rats of four experimental groups were sacrificed and renal tissue samples were harvested at different time point respectively, the control group rats were treated in Xining city (2260 m) as well. The concentration of plasma antidiuretic hormone (ADH) was measured by radioimmunity method. The expression of AQP2 mRNA and proteins was evaluated by real-time fluorescent quantitative-PCR, Western blot and immunofluorescence assay. Results The concentration of plasma ADH was decreased at 24 h and was only 28.5% of that of control group, reaching the lowest concentration at 48 h [(86.94±6.49) μg/L vs (302.5±310.48) μg/L], then it increased gradually and was similar to the control group at 7 d [(306.46±11.14) μg/L vs (302.53±10.48)μg/L, P＞ 0.05]. There were significant differences of the control group with 24 h, 48 h and 72 h groups, respectively[(302.53± 10.48) μg/L vs (142.46±10.57)μg/L, (86.94±6.49)μg/L, (169.65±11.15) μg/L respectively, P＜0.01]. The change of AQP2 gene expression level was consistent with the change of ADH. It was decreased at the begining when exposure to altitude and it reached its lowest level at 48 h. It was then returned to high level similarly to that of the control group at 7 d (0.09±0.01 vs 0.09± 0.008, P＞0.05 ). There were significant differences of the control group with 24 h, 48 h and 72 h group, respectively (0.09±0.008 vs 0.04±0.005, 0.03±0.002, 0.04±0.003 respectively, P＜0.01 ). Conclusions AQP2 expression in the renal collecting duct of SD rats is altered over the period exposed to altitude. It is decreased in the early hypoxia period, and is increased in later period. This change may be related to the intensity of hypoxia, which is mediated by a potential adaptation mechanisms against hypoxia caused by high altitude.