【Abstract】Objective To explore the changes in renal function, renal injury biomarkers, and renal pathology in rats over time after entering a simulating low-pressure and low-oxygen environment from the plains to the plateau. Methods 30 male Sprague-Dawley rats were divided into 5 groups randomly, with 6 rats in each group. The control group was placed outside the chamber under normal pressure and oxygen conditions. The experimental groups were placed in a low-pressure and low-oxygen(LPLO) chamber to simulate a plateau environment at 5000m above sea level, living in the chamber for 3 days, 7 days, 14 days, and 28 days respectively. Observe the renal injury biomarkers of each group: serum creatinine (CRE), serum cystatin C (CysC), serum neutrophil gelatinase-associated lipocalin (NGAL), serum kidney injury molecule-1(KIM-1) and serum interleukin-18 (IL-18) levels. HE staining and PAS staining is used to observe the pathological changes of kidney injury. Results Compared with the control group, the levels of NGAL, KIM-1, CysC, and CRE in the experimental group were significantly increased (all P<0.05). The average diameter of glomeruli was significantly reduced in the LPLO 3day group, significantly increased in the LPLO 14day group (both P<0.05). The PTC/tubule was significant decreased. The renal tubular injury score and OM congestion score were significant increased (both P<0.05). Regression analysis showed that PTC/tubule was linearly negatively correlated with the duration of low-pressure and low-oxygen, while CRE, CysC, and pathological indicators (mean glomerular diameter, OM congestion score, and renal tubular injury score) were curvilinearly correlated with the duration of low-pressure and low-oxygen (all P<0.05). For the variables that showed curvilinear correlation, restricted cubic splines (RCS) analysis was used: each curve exhibited an "inverted L" shape, with inflection points occurring on the 7th day, indicating that the rate of increase for all indicators was highest within the first 7 days of low-pressure and low-oxygen, and the rate of increase slowed from 7 days to 28 days. Conclusions After simulating entering the plateau environment from the plain, there were significant damage in the kidney in terms of structure and function, and the kidney had a self-adaptive adjustment process toward the plateau environment.