This study was conducted to evaluate the protective effect of dexmedetomidine on nephrotoxicity and the mechanism of renoprotection following vancomycin-induced nephrotoxicity in rats.Thirty-two albino Wistar rats were divided into four groups. The control group received intraperitoneal (IP) physiological saline solution, the vancomycin (VMC) group received IP 200 mg/kg vancomycin, the dexmedetomidine (DEX) group received IP 5 µg/kg dexmedetomidine, and the vancomycin and dexmedetomidine (VMC+DEX) group received IP 200 mg/kg vancomycin followed by IP 5 µg/kg dexmedetomidine 20 min after the vancomycin injection. On the 8th day of the experiment, histopathological and biochemical parameters were assessed.Creatinine levels were significantly higher in VMC and VMC+DEX groups. The endothelin-1 level was significantly higher in VMC group. Nitric oxide levels were statistically lower in VMC and VMC+DEX groups. Histopathologic assessments revealed that the extent of renal damage was significantly higher in group VMC (n = 4 with damage of Grade 3) compared to group VMC+DEX (n = 0 with damage of Grade 3).It was determined that dexmedetomidine can reduce the extent of renal damage by preventing the elevation of vasoconstrictor agents (Tab. 2, Fig. 1, Ref. 36).