Endothelial cell damage and impaired angiogenesis substantially contribute to the progression of chronic renal failure (CRF). The effect of endothelial progenitor cell (EPC) treatment on the progression of CRF is yet to be determined. We performed 5/6 nephrectomy to induce CRF in C57BL/6 mice. EPCs were isolated from bone marrow, grown in conditioned medium, and characterized with surface marker analysis. The serial changes in kidney function and histological features were scrutinized in CRF mice and EPC-treated CRF (EPC-CRF) mice. Adoptively transferred EPCs were present at the glomeruli and the tubulointerstitial area until week 8 after transfer. In CRF mice, renal function deteriorated steadily over time, whereas the EPC-CRF group showed less deterioration of renal function as well as reduced proteinuria along with a relatively preserved kidney structure. Renal expression of proinflammatory cytokines and adhesion molecules was already decreased in the EPC-CRF group at the early stage of disease, at which point the renal function and histology of CRF and EPC-CRF mice were not different. Angiogenic molecules including VEGF, KDR, and thrombospondin-1, which were decreased in the CRF group, were restored by EPC treatment. In conclusion, EPCs trafficked into the injured kidney protected the kidney from the inflammatory condition and consequently resulted in functional and structural renal preservation. Our study suggests EPCs as a potential candidate for a novel therapeutic approach in CRF.