Retinoic acid (RA) is a major chemopreventive agent which exerts strong anti-tumor activity partly by trans-repressing the Wnt/beta-catenin signaling pathway in some tumor cell lines. However, the definite mechanism of RA trans-repression of the Wnt/beta-catenin signaling pathway has not been elucidated clearly. In this work, we found that all-trans retinoic acid (ATRA) significantly inhibited proliferation of glioma cells, accompanied by up-regulation of expression of Axin and altered subcellular distribution of beta-catenin. Transfecting C6 cells with rAxin further confirmed that increased expression of Axin is obligate for inhibition of proliferation and the increase of the cytoplasmic beta-catenin. Our results suggested that Axin might play an important role in RA-mediated anti-proliferative effects of glioma cell lines.