BACKGROUND: N-methyl-D-aspartate (NMDA) antagonists can be useful as preemptive analgesic agents and effective in reducing central sensitization. The purpose of this study was to evaluate the preemptive effect of intravenous (IV) ketamine on the behavioral responses between a pre- versus post-formalin test in a rat model. METHODS: Sprague-Dawley rats (250 - 300 g) were prepared with a PE-50 indwelling IV catheter to receive either saline or ketamine. Rats received ketamine 1 mg/kg intravenously through a catheter either 1 min before or 5 min after formalin. The formalin test was performed with 5% formalin 100nl. All rats were randomly divided into one of three groups; a control (n = 8), pre-treatment (n = 7), or post-treatment (n = 7) group. Pain related behaviors were quantified by counting the numbers of flinching of the injected paw for 60 minutes. RESULTS: Intraplantar formalin injection produced a biphasic (phase 1, 0 - 10 minutes; phase 2, 10 - 60 minutes after formalin injection) appearance of flinching behavior in the control, pre-treatment, and post- treatment groups. The pre-treatment group showed less flinching in phase 2 than the control group (P < 0.05), but the post-treatment group didn't. CONCLUSIONS: These results suggest that pre-treatment of IV ketamine 1 mg/kg showed a preemptive analgesic effect.