We tested our hypothesis that a commonly used anesthetic, ketamine, may offer benefits to protect animals from spinal cord injury, using the ischemia/reperfusion (I/R) injury rabbit model in a randomized controlled study. We used 24 white adult Japanese rabbits from the animal facility at the Medical College of Wuhan University. The rabbits were randomly assigned to one of three groups, eight rabbits per group: group I, sham-operation group; group II, I/R group; group III, I/R with ketamine treatment group. Spinal cord ischemia was induced by infrarenal aortic cross-clamp for 45 min in group II and group III, and ketamine was intravenously infused at 10 mg/kg in 15 mL 0.9% sodium chloride at a speed of 1.5 mL/min to animals in group III, once at 10 min before aortic clamping and once at the onset of reperfusion. Postoperative neurological function, electromyography of rear limbs, histopathology, malondialdehyde (MDA) levels, and superoxide dismutase (SOD) activity in the spinal cord were assessed in all animals. Compared with the control group I, group II showed significant I/R injury-induced changes in neurological function scores, histopathology, and electromyography (p < 0.01). However, group III with ketamine treatment significantly reversed the changes in all these parameters (p < 0.01). At the same time, the I/R-induced increase in MDA content observed in group II was also significantly reduced in group III (p < 0.01), and the I/R-induced decreases in SOD activity were also significantly prevented in group III (p < 0.01). After ketamine treatment, all parameters examined in group III were not significantly different from those obtained in group I. Ketamine showed potent protective effects against spinal cord I/R injury in the rabbit model and protected loss of antioxidant activity in spinal cord tissues.