In order to study the effect of the cellular repressor of E1A-stimulated genes (CREG) on differentiation and migration of human vascular smooth muscle cells (VSMCs)-HITASY, the full length human sense and antisense-CREG cDNA retroviral vectors, pLNCX₂( ＋ )/CREG and pLXSN( － )/CREG, were constructed. Western blot and immunoflourescence analysis showed that the expression of CREG and SM α -actin increased in HITASY after infection with pLNCX₂( ＋ ) /CREG. The migration of HITASY infected with pLNCX2( ＋ )/CREG obviously enhanced compared with that of normal HITASY and pLXSN( － )/CREG cells showed by scrape-wounding and time-lapse analysis. Moreover, CREG over-expression increased the secretion of MMPs in HITASY tested by Western blot. Gelatin SDS-PAGE zymography analysis revealed that the activities of MMPs also increased in HITASY infected with pLNCX₂( ＋ )/CREG . On the other hand, the opposite effects were observed when CREG expression decreased by using antisense pLXSN( － )/CREG . These results suggest that CREG may be able to induce the VSMCs differetiation and promote the VSMCs migration in the meantime.