Epithelial to mesenchymal transition (EMT) is a physiological phenomenon in mammalian embryogenesis by which epithelial cells become mesenchymal stem cells. Studies have indicated that an inappropriate EMT plays a key role in a variety of pathogenic processes such as embryonic development and tumor metastasis. Moreover, recent studies have indicated EMT also plays an important role in renal fibrosis. In the current study, glucose and angiotensin II promoted EMT in podocytes as well as changes in the cellular morphology of podocytes. A high concentration of glucose and angiotensin II also promoted podocyte movement and migration. Moreover, a high concentration of glucose and angiotensin II promoted TCF8 expression. Inhibiting TCF8 expression with siRNA reversed EMT in podocytes in the presence of a high concentration of glucose and angiotensin. Inhibiting TCF8 expression also reversed changes in cellular morphology and podocyte movement and migration. Therefore, glucose and angiotensin II may promote EMT in podocytes via TCF8.