Inflammatory response occurs when tissues are injured by pathogens, trauma, toxins, or heat. Lectins are proteins that recognize and bind reversibly to glycans and glycoconjugates and can modulate inflammatory responses in in vitro and in vivo models. As such, this study aimed to evaluate the potential of an anti-inflammatory lectin isolated from Machaerium acutifolium seeds (MaL) in mice and LPS-stimulated macrophage models. The protein was solubilized in sterile saline (0.9 % NaCl) immediately before treatment of mice by intraperitoneal routes at doses of 0.02 mg/kg, 1 mg/kg and 5 mg/kg. MaL significantly decreased inflammation in the formalin test, inhibited cell migration in experimental models of carrageenan-induced peritonitis, and blocked the formation of paw edema induced by carrageenan and dextran. In vitro studies showed that MaL downregulated the proinflammatory cytokine genes inducible nitric oxide synthase (iNOS) and tumor necrosis factor-alpha (TNF-alpha), but upregulated the anti-inflammatory IL-10 gene in LPS-stimulated macrophages. Therefore, this study suggests that MaL has an anti-inflammatory effect relative to modulated levels of pro- and anti-inflammatory cytokines, indicating that MaL can be used as a potential therapeutic agent in cellular inflammatory events.