Recent data suggest that AKT2, one of AKT isoforms, plays an important role in tumorigenesis of human cancers. However, little evidence exists to show the mechanism of AKT2 involved in tumorigenesis. In this study, we show that AKT2 protein expression increased significantly in high grade gliomas in comparison to low grade gliomas and correlated with the expression of NFkappaB, BCL2, MMP2 and MMP9 by immunostaining. Further, down-regulation of AKT2 expression by antisense AKT2 induced glioma cell apoptosis mediated by NFkappaB and BCL2. In addition, decreased MMP2 and MMP9 expression in AKT2 knocked-down glioma cells was subsequently detected, consistent with the decreased invasion. These findings indicate that AKT2 expression is associated with more advanced and especially aggressive gliomas and critical for cell survival and invasion.