The present study investigates the antinociceptive properties of lupeol inmodels of inflammatory and post-operative pain, as well as its mechanisms of action. The effects of lupeol were tested against acetic acid-induced writhing, formalin test, carrageenan-induced hyperalgesia, and post-operative pain model. Cytokine levels were determined by ELISA. Mice motor performance was evaluated in the rota rod and open-field tests. Pre-treatment of mice with lupeol (5–100mg/kg IP) produced a dose-related inhibition of writhing in mice. The maximal antinociception produced by lupeol (60mg/kg) was unaffected in mice pre-treated with yohimbine (a2 adrenoceptor antagonist; 2mg/kg IP), L-arginine (substrate for nitric oxide synthase; 600mg/kg IP), glibenclamide (the KATP-channel blocker; 2mg/kg IP), and methysergide maleate (serotoninergic receptors antagonist; 5mg/kg IP). Furthermore, lupeol (25–100mg/kg) inhibited the late phase of formalin test. Pre-treatment with lupeol (50 and 100mg/kg) inhibited the hyperalgesia and the local increase in tumor necrosis factor-a (TNF-a) and interleukin-1b (IL-1b) levels induced by carrageenan. In contrast, lupeol did not inhibit the post-operative pain. Lupeol-treated mice did not show any motor performance alterations or apparent systemic toxicity. Our results demonstrate that lupeol has consistent antinociceptive properties during inflammatory pain, but not post-operative pain, acting through the inhibition of IL-1b and TNF-a production.