is probably the most common medicinal mistletoe plant in Brazil, and has been used in folk medicine as an anti-inflammatory agent and for cleaning skin wounds. Our proposal was to evaluate the anti-inflammatory activity of ethanol leaf extract and provide further insights of how this biological action could be explained using and assays. anti-inflammatory activity was preliminarily investigated in lipopolysaccharide/interferon gamma-stimulated macrophages based on their ability to inhibit nitric oxide production and tumor necrosis factor-alpha. anti-inflammatory activity of ethanol leaf extract was investigated in the mice carrageenan-induced inflammation air pouch model. The air pouches were inoculated with carrageenan and then treated with 50 and 100 mg/kg of ethanol leaf extract or 1 mg/kg of dexamethasone. Effects on the immune cell infiltrates, pro- and anti-inflammatory mediators such as tumor necrosis factor-alpha, interleukin 1, interleukin 10, and nitric oxide, were evaluated. The chemical composition of ethanol leaf extract was characterized by LC-MS/MS. ethanol leaf extract significantly decreased the production of nitric oxide and tumor necrosis factor-alpha in macrophages and did not reveal any cytotoxicity. ethanol leaf extract significantly suppressed the influx of leukocytes, mainly neutrophils, protein exudation, nitric oxide, tumor necrosis factor-alpha, and interleukin 1 concentrations in the carrageenan-induced inflammation air pouch. In conclusion, ethanol leaf extract exhibited prominent anti-inflammatory effects, thereby endorsing its usefulness as a medicinal therapy against inflammatory diseases, and suggesting that ethanol leaf extract may be a source for the discovery of novel anti-inflammatory agents.