Chronic kidney disease (CKD) is a common complication of diabetes mellitus. CKD is an irreversible process that eventually leads to end-stage renal failure, a devastating condition that necessitates the patients to be dependent on life-long treatments with dialysis or renal transplantation. Renal tubulointerstitial fibrosis is a final common pathway that leads to progressive renal injury in a range of conditions, including diabetic nephropathy (DN). Epithelial-to-mesenchymal transition (EMT) has been implicated in the accelerated fibrogenesis that is seen in diabetic nephropathy. The process of EMT is induced in epithelial cells to lose its cell-to-cell adhesion and transform to mesenchymal-like cells. Similary, fibroblasts can be activated into myofibroblasts, which expresses α-smooth muscle actin. TGF-β1 induces the transcription factor Snail, which is involved in EMT, in cancer cells. TGF-β1-triggered EMT is an important process in DN. Thus, we wished to understand the role of Snail in high glucose and AII-induced effects in renal cells. We found that Angiotensin II (AII) and high glucose induce (reactive oxygen species, ROS) to stimulate TGF-β1 activity. TGF-β1 also induced Snail gene expression by stimulating ROS. Snail did not regulate cell cycle but induced the process of EMT in NRK-49F cells. Moreover, both BMP-7 and Estrogen did not attenuate TGF-β1-induced Snail expression. 2D-gel electrophoresis and mass spectrometry showed that 3 proteins were regulated by the TGF-β1-Snail pathway. We also found that TGF-β1 induced Snail expression through the mTOR pathway. We concluded that the ROS- TGF-β1-ROS- Snail pathway and the TGF-β1- mTOR - Snail pathway are involved in high glucose-induced effects in renal cells.