The purpose of this study was to investigate the renal protective efficacy of propofol, ketamine, and ketofol in an ischemia/reperfusion injury (IRI) model experimentally induced in rats. Thirty-five male Sprague-Dawley rats were randomly assigned into five groups: sham (Group 1), control (Group 2), ketamine (Group 3), propofol (Group 4), and ketofol (Group 5). Following administration of intramuscular ketamine hydrochloride anesthesia, the left renal hilum was exposed to 60-minutes clamping. Ketamine (Group 3), propofol (Group 4), and ketofol (Group 5) were administered 15 min prior to reperfusion. After six hours of reperfusion, the left kidneys were harvested for histological injury scoring. Mean histopathology scores were 0.42±0.53 in group 1 (Sham), 2.97±0.21 in group 2 (Control), 2.68±0.15 in group 3 (Ketamine), 2.40±0.16 in group 4 (Propofol), and 2.51±0.22 in group 5 (Ketofol). The score in group 4 (Propofol) was significantly lower than those in groups 2 (control) and 3 (Ketamine) (P=.002 and P=.0120, respectively), but did not differ significantly from that in group 5 (Ketofol) (P=.347). The score in group 5 (Ketofol) was significantly lower compared to group 2 (control) (P=.006), but no significant difference was determined with Group 3 (Ketamine) (P=.137). No significant difference was also observed between Group 3 (Ketamine) and Group 2 (control) (P=.021). The study results indicated no superiority of ketofol over ketamine or propofol against renal IRI. However, the renal protective effect of propofol against IRI was greater than that of ketamine.