Aim To observe the effects of endothelial progenitor cells (EPC) conditional medium on the proliferation of vascular smooth muscle cells (VSMC) induced by angiotensin Ⅱ(AngⅡ).Methods Mononuclear cells were isolated from fresh cord blood by 3% Gelatin and density gradient centrifugation. Isolated mononuclear cells were cultured in EBM-2 medium. Flow cytometry and indirect immunofluorescence revealed that EPC expressed hematopoietic progenitor cell-surface antigens as well as endothelial cell-surface antigens. After preparating early endothelial progenitor cell conditioned medium (E-EPC-CM), late endothelial progenitor cell conditioned medium (L-EPC-CM) and human umbilical vein endothelial cell conditioned medium (HUVEC-CM), the effect of E-EPC-CM, L-EPC-CM and HUVEC-CM on AngⅡ-induced DNA synthesis, total protein expression, cell survival and cycle progress was assessed by BrdU incorporation, total protein content, MTT assays and flow cytometry. Western blot were performed to analyze the effect of E-EPC-CM on the AngⅡ-induced phosphorylations of ERK, JNK, p38 MAPK and the expressions of proto-oncogene c-myc and c-fos.Results The DNA synthesis, total protein contents and cell survival obviously increased in AngⅡ (10^-6mmol/L) induced VSMC for 48 h compared with control group, while pretreatment with E-EPC-CM, L-EPC-CM and HUVEC-CM resulted in significant inhibitions in DNA synthesis, total protein content, and cell survival compared with the control groupThe percentage of S phase cells significantly increased, while the percentage of cells in G₁ phase decreased remarkably compared with control group, pretreatment with E-EPC-CM, L-EPC-CM, or HUVEC-CM led to sustained decrease in the percentage of cells in S phase and sustained increase in the percentage of cells in G₁ phase after 48 h of stimulation with AngⅡ Western Blot showed that AngⅡ time dependently induced phosphorylation of p38, JNK, ERK and significantly increased the expressions of c-myc and c-fos after AngⅡ stimulation in VSMC, while pretreatment with E-EPC-CM showed marked inhibitory effect on the AngⅡ-induced phosphorylations of these MAPK and the expressions of proto-oncogene c-myc and c-fos. E-EPC-CM showed strongest inhibitory effect among all treatment groups.Conclusion EPC may inhibit AngⅡ-induced proliferation and phenotype transformation of VSMC through inactivating MAPKs signaling pathways as well as by reducing the expressions of proto-oncogene c-myc and c-fos.