OBJECTIVE: This study was conducted to evaluate the protective effect of dexmedetomidine on nephrotoxicity and the mechanism of renoprotection following vancomycin-induced nephrotoxicity in rats. METHODS: 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. RESULTS: Creatinine levels were signifi cantly higher in VMC and VMC+DEX groups. The endothelin-1 level was signifi cantly 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 signifi cantly higher in group VMC (n = 4 with damage of Grade 3) compared to group VMC+DEX (n = 0 with damage of Grade 3). CONCLUSION: 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).