Objective and design β-Caryophyllene (BCP) is a sesquiterpene that binds to the cannabinoid 2 (CB 2 ) receptor and exerts anti-inflammatory effects. In this study, we investigated the anti-inflammatory effect of BCP and another CB 2 agonist, GP1a in inflammatory experimental model induced by Mycobacterium bovis (BCG). Methods C57Bl/6 mice were pretreated orally with BCP (0.5–50 mg/kg) or intraperitonealy with GP1a (10 mg/kg) 1 h before the induction of pleurisy or pulmonary inflammation by BCG. The direct action of CB 2 agonists on neutrophils function was evaluated in vitro. Results β-Caryophyllene (50 mg/kg) impaired BCG-induced neutrophil accumulation in pleurisy without affecting mononuclear cells or the production of TNF-α and CCL2/MCP-1. However, BCP inhibited CXCL1/KC, leukotriene B 4 (LTB 4 ), IL-12, and nitric oxide production. GP1a had a similar effect to BCP. Preincubation of neutrophils with BCP (10 µM) impaired chemotaxis toward LTB 4 and adhesion to endothelial cells stimulated with TNF-α, and both, BCP and GP1a, impaired LTB 4 -induced actin polymerization. Conclusion These results suggest that the CB 2 receptor may represent a new target for modulating the inflammatory reaction induced by mycobacteria.