Objective To explore time-related changes in renal function, renal injury biomarkers, and renal pathology in rats entering a low-pressure and low-oxygen (LPLO) environment simulating moving from the plains to a plateau. Methods Thirty male Sprague-Dawley rats were divided randomly into five groups (n=6 rats per group). Rats in the Control group were placed outside the chamber under normal pressure and oxygen conditions. Rats in the experimental groups were placed in an LPLO chamber to simulate a plateau environment at 5000 m above sea level, and were maintained in the chamber for 3, 7, 14, and 28 days, respectively. Serum levels of creatinine (CRE), cystatin C (CysC), neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and interleukin-18 (IL-18) were measured as biomarkers of renal injury. Pathological changes in the kidney were observed by hematoxylin and eosin and periodic acid-Schiff staining, with quantitative assessment of the following parameters: average glomerular diameter, peritubular capillary (PTC) density per tubule, tubular injury score, and outer medulla (OM) congestion score. Results NGAL, KIM-1, CysC, and CRE were significantly increased in the experimental compared with the Control group (all P<0.05). The average glomerulus diameter was significantly reduced in the LPLO 3 d group and significantly increased in the LPLO 14 d group (both P<0.05). The peritubular capillary (PTC)/tubule ratio was significantly decreased. The renal tubular injury and OM congestion scores were significantly increased (both P<0.05). Regression analysis showed that PTC/tubule was linearly negatively correlated with the LPLO duration, while CRE, CysC, and pathological indicators (mean glomerular diameter, OM congestion score, renal tubular injury score) were curvilinearly correlated with the duration of LPLO (all P<0.05). Variables with a curvilinear correlation were analyzed using restricted cubic splines(RCS). Each curve exhibited an inverted-L shape, with inflection points on day 7, indicating that the rate of increase of all indicators was highest within the first 7 days of LPLO, and the rate of increase then slowed from 7 days to 28 days. Conclusions A simulated move from a plains to a plateau environment was associated with significant structural and functional renal damage, but the kidneys then showed a self-adaptive adjustment process towards the plateau environment.