Abstract Objectives This study reports the in vivo anti-inflammatory and antioxidative effects of the methanolic extract of the aerial parts of Mitracarpus frigidus (MFM) and its chemical fingerprint. Methods The acute anti-inflammatory activity was performed using the carrageenan-induced paw oedema and peritonitis, ear oedema induced by croton oil and ethyl phenylpropiolate methods. Total COX, COX-1 and COX-2 expression was also evaluated. Chronic activity was determined by cotton pellet granuloma model. The antioxidative activity was assessed using liver tissue malondialdehyde, catalase and myeloperoxidase activities. Key findings M . frigidus showed an intense acute anti-inflammatory action (100 and 300 mg/kg) in a nondose-dependent manner with selective inhibition of COX-2 expression. This activity may be also related to the strong antioxidative effect observed. By the other side, the chronic anti-inflammatory activity of MFM was not expressive. Kaempferol, kaempferol-O-rutenoside, rutin, ursolic acid and psychorubrin were identified in MFM. Conclusions The anti-inflammatory activity of MFM was probably due to inhibition of COX expression in a selective manner for COX-2. Other mechanisms, such as inhibition of inflammatory mediators and of the oxidative stress were possibly involved in the effects observed. To the best of our knowledge, it is the first time those activities are reported for M. frigidus.