Mesenchymal stem cells (MSC) are of clinical interest due to their potential use in autologous transplantation. A lot of clinical trials using MSCs are accomplished, and lots of others are being under examination. The earliest detectable signs are microalbuminuria and histopathological changes including extracellular matrix deposition, glomerular basement membrane thickening, glomerular and mesangial expansion. Later on macroalbuminuria appears, followed by a progressive decline in glomerular filtration rate and therefore the loss of glomerular podocytes, tubulointerstitial fibrosis, glomerulosclerosis and arteriolar hyalinosis. Tight glycemic and hypertension controls remain the key factors for preventing or arresting the progression of DN. Nevertheless, despite considerable educational effort to regulate the disease, a big number of patients not only develop DN, but also reach chronic renal disorder the most therapeutic effects of MSCs are now attributed to the stimulation of several endogenous repair processes in injured tissues in vivo by secreted factors also because the modulation of immune reaction , which translates into a positive outcome of MSC-based therapies.