Objective:To investigate the antinociceptive effect of tingenone on inflammatory pain, as well as and the involvement of the cannabinoid receptors type 2 (CB2) and spinal microglia in this process. Methods:Male Swiss mice were subjected to inflammatory pain induced by intraplantar injection of carrageenan. The nociceptive threshold was measured by von Frey filaments test. Tingenone was administered orally 60 min before carrageenan injection. To evaluate the involvement of CB2 receptor, endocannabinoids, and microglia, AM630 (a CB2 receptor antagonist), MAFP (an inhibitor of an enzyme that hydrolyses endocannabinoids), and minocycline (a microglial inhibitor) were given intrathecally 20 min before tingenone administration. In addition, an immunofluorescence assay was used to evaluate CB2 receptor and CD11B (a microglial marker) expression in the spinal cord dorsal horn. Results:Tingenone significantly reduced carrageenan-induced hyperalgesia, which was reversed by pretreatment with AM630. MAFP and minocycline potentiated and prolonged the tingenone-induced antinociception. CD11B expression was increased in the spinal cord dorsal horn of mice with inflammatory pain pretreated with tingenone, which was reduced by AM630, MAFP, and minocycline. Conclusions:CB2 receptors and endocannabinoids participate in the tingenone-induced antinociception which may involve the inhibition of microglia at spinal level.