Perillyl alcohol (PA) is a natural compound found in essential oils. In this study, the antinociceptive activity of PA was evaluated using acetic acid and formalin tests. The involvement of the opioid system in its mechanism of action was investigated. Potential histological changes in the hippocampus and striatum were also assessed. In the acetic acid induced writhing tests, the mice pretreated with PA exhibited significant reductions in writhing. PA inhibited formalin injected paw licking response, and naloxone partially reversed the antinociceptive activity of perillyl alcohol during the writhing test. And as for the histopathological evaluation, PA did not cause significant tissue changes. This study suggests that PA possesses antinociceptive effects without significant hippocampus or striatum neurotoxicity, and that its activity involves opioid.