Previous studies have demonstrated that endothelial progenitor cells (EPCs) could delay the progress of vascular remodeling in blood vessel–proliferating diseases. The proliferation of vascular smooth muscle cells (VSMCs) is a pivotal factor in cardiovascular diseases. In this study, we investigated whether EPCs could inhibit the Angiotensin II (Ang II)–induced proliferation of VSMCs. The effect of early EPC-conditioned medium (E-EPC-CM), late EPCs-CM (L-EPC-CM), and HUVEC-CM on Ang II–induced proliferation of VSMCs was assessed by BrdU incorporation, total protein content, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays, and flow cytometry. Reverse transcriptase–polymerase chain reaction and Western blot were performed to analyze the effect of different CMs on Ang II–induced phosphorylations of ERK, JNK, p38, and NF-κB subunit p65 and the expressions of c-myc and c-fos. E-EPC-CM, L-EPC-CM, and HUVEC-CM significantly inhibited the Ang II–induced DNA synthesis, total protein expression, cell survival, and cell cycle progress of VSMCs. Furthermore, E-EPC-CM significantly inhibited the Ang II–induced phosphorylation of ERK, JNK, p38, and p65 (nuclear translocation of p65) and the expressions of c-myc and c-fos. Taken together, these data suggested that EPCs may delay the progress of vascular remodeling in blood vessel–proliferating diseases by inhibiting Ang II–induced proliferation of VSMCs through inactivating MAPKs and NF-κB signaling pathways and by reducing the expressions of c-myc and c-fos.