Abstract: Objective： To observe the effect of xenon exposure on gentamicin-induced acute kidney injury. Methods： 48 male Wistar rats were randomly divided into four groups as follows: the model group, where rats were given intraperitoneal (i.p.) injection of gentamicin sulfate solution 100 mg/(kg·d) for 7 days; the control group, where rats were intraperitoneally administrated physiological saline (0.9%) for 7 days; the N₂+gentamicin group (N₂+gent) and the Xenon+gentamicin group (Xe+gent), where rats were pretreated with 70% nitrogen or 70% xenon balanced with 30% oxygen for 2 h, followed by 7 days of gentamicin treatment initiated 24 h later, and repeatedly treated with 70% nitrogen or 70% xenon for 30 min on day 2, 4, and 6 during the 7-day administration of gentamicin. Renal function, renal morphology and, oxidative stress indexes were collected respectively on day 2, 4 after the last gentamicin injection for assay (n=6 at each time point per group). serum creatinine (Scr) and blood urea nitrogen (BUN) were examined. The kidney tissue was stained by H-E. Renal malondialdehyde (MDA) and renal superoxide dismutase (SOD) activity were measured. Results： Compared with the control group, Scr and BUN levels were significantly increased on day 2, 4 after last gentamicin injection in the model group and N₂+gent group, renal tubular damage index increased significantly, MDA concentration, the oxidative stress index, were also higher than that of the control group, and the activity of SOD decreased, all showing obvious decline in renal function(P< 0.01). Compared with the model group and the N₂+gent group, the degree of renal injury was significantly reduced in the Xe+gent group: Scr and BUN concentration decreased, renal tubular damage index decreased, the MDA concentration in renal tissue decreased, and SOD activity increased significantly(P< 0.01). Conclusions： Xenon treatment can significantly reduce gentamicin-induced acute kidney injury in rats.