Transforming growth factor-beta(1) (TGFbeta(1)) is recognized as both a fibrogenic and inflammatory cytokine and plays a critical role in the kidney pathophysiology. The dysregulation of TGFbeta(1) has been linked with the development of diabetic nephropathy. Connective tissue growth factor (CTGF) is a fibrogenic cytokine and is recognized as a downstream mediator of TGFbeta(1) in kidney fibrosis. TGFbeta(1) is involved in immunomodulation and fibrosis in the kidney. However, CTGF plays a more specific role in the fibrogenic pathways in the kidney proximal tubule cells. Moreover, CTGF facilitates TGFbeta(1) signaling and promotes renal fibrosis. This suggests CTGF could be a potential target for kidney fibrosis. Long-term inhibition and targeting TGFbeta(1) directly is problematic, therefore, a more fruitful direction targeting diabetic nephropathy may involve the development of therapeutic strategies specifically targeting CTGF.