Epithelial–mesenchymal transition (EMT) is an important cellular event in organogenesis, cancer and renal tubulointerstitial fibrosis. Transforming growth factor-beta1 (TGF-beta1) is the key inducer of EMT and the p38 mitogen-activated protein kinases (p38 MAPK), an major intracellular signal transduction pathway is involved in TGF-beta1-induced EMT. Astrocyte elevated gene-1 (AEG-1) represents an chief genetic determinant regulating multiple events in tumorigenesis. Our present study is to explore the role of AEG-1 in TGF-beta1-induced p38 MAPK activation and EMT process in human renal tubular epithelial (HK-2) cells. The protein expressions of AEG-1, the markers of EMT and p38 phosphorylation were measured by Western blot. The protein expression of AEG-1 was increased in HK-2 cells treated with TGF-beta1. Knockdown of AEG-1 potently inhibited phosphorylation of p38 MAPK and reversed TGF-beta1-induced EMT. Over-expression of AEG-1 via AEG-1 transfection elicited p38 MAPK phosphorylation and promoted EMT. The effects of AEG-1 during EMT were blocked by a p38-specific inhibitor. Our findings suggest that AEG-1 plays an important role in TGF-beta1-induced EMT through activation of p38 MAPK in proximal tubular epithelial cells.