1,25-(OH)2D3, the active metabolite of vitamin D, regulates immune responses in addition to its role in calcium, phosphorus, and bone metabolism. Recent data suggests that 1,25-(OH)2D3 blocks dendritic cell maturation influencing the development of regulatory T cells. High dose 1,25-(OH)2D3 monotherapy is effective at delaying acute rejection. The vitamin D receptor (VDR), which functions as a transcription factor, forms a complex with Smad 3, a TGFb-1 signaling protein, in rat renal lysates for treated recipients. 1,25-(OH)2D3 significantly prolonged graft survival, limited the degree of intersitial fibrosis and glomerulosclerosis, decreased urinary protein and altered Smad and MMP expression in a rat renal model of CAN. In a retrospective clinical study, that cadaveric renal transplant recipients with renal insufficiency placed on calcitriol demonstrate improved renal function and improved graft survival. 1,25-(OH)2D3 may regulate TGFb-1-mediated ECM deposition.