ABSTRACT. The aim of this study was to investigate the neuroprotective effects of ketamine during acute spinal cord injury in rats. Sprague Dawley (SD) rats (N = 70) were randomly divided into three groups: sham-operated (N = 10), control (N = 30), and treatment (N = 30) groups. The moderate spinal cord injury model was established. After injury, the sham-operated group received no drug, the treatment group received intraperitoneal ketamine injections, and the control group received intraperitoneal normal saline injections. Serum levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and spinal cord malondialdehyde (MDA) were assessed, and nerve cell apoptosis was evaluated in each group at varying time points. After spinal cord injury, TNF-α, IL-6, and MDA levels, and the number of TUNEL-positive cells among 2500 cells significantly increased (P < 0.05). Further, compared with the control group, the treatment group showed significantly lower TNF-α, IL-6, and MDA levels, and fewer TUNEL-positive cells among 2500 cells at each time point (P < 0.05). Our data indicate that ketamine exerts a neuroprotective effect on injured spinal cord.