<ns4:p><ns4:bold>Background: </ns4:bold>Several ethnobotanical and ethnopharmacological studies have shown the therapeutic potential of plants from the genus <ns4:italic>Tabebuia</ns4:italic>, which have long been used in traditional medicine in rural areas of South America, for the treatment of several human diseases. This study aimed to evaluate the Nrf2-mediated antioxidant activity of the inner bark extracts obtained from <ns4:italic>Tabebuia rosea</ns4:italic> and <ns4:italic>Tabebuia chrysantha</ns4:italic>.</ns4:p><ns4:p> <ns4:bold>Methods: </ns4:bold>The antioxidant activity of extracts obtained from the inner bark of <ns4:italic>T. rosea</ns4:italic> and <ns4:italic>T. chrysantha</ns4:italic> was evaluated using the Oxygen radical absorbance capacity (ORAC) technique. The effect of extracts on the viability of HepG2 cells was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) method. The translocation of Nrf2 to the nucleus after exposure of HepG2 cells to the extracts and controls (α-lipoic acid, curcumin and hydrogen peroxide) was evaluated using the Nrf2 transcription factor kit. Induction of the Nrf2-mediated antioxidant response gene (<ns4:italic>NQO1</ns4:italic>) was evaluated by real-time PCR.</ns4:p><ns4:p> <ns4:bold>Results: </ns4:bold>The ethyl acetate extract obtained from both species displayed the highest ORAC activity (12,523 and 6,325 µmoles Eq Trolox/g extract, respectively). In addition, the extracts had the ability to activate and to translocate Nrf2 to the nucleus, as well as to induce the expression of <ns4:italic>NQO1</ns4:italic>.</ns4:p><ns4:p> <ns4:bold>Conclusion:</ns4:bold> These results indicate that the ethyl acetate extracts obtained from the inner bark of <ns4:italic>T. chrysantha</ns4:italic> and <ns4:italic>T. rosea</ns4:italic> have an important antioxidant effect mediated by Nrf2 activation, and could be used as a new source of natural antioxidants.</ns4:p>