Cellular repressor of E1A-stimulated genes (CREG) has been shown to be ubiquitously expressed in human and mouse tissues. However, its physiological functions and possible involvement in pathological processes remain unknown. To explore pathogenesis of vascular remodeling and possible role of CREG, we established an injury model of the mouse carotid artery in the present study. High-resolution small-animal ultrasound, Masson staining, immunohistochemistry, RT-PCR and Western-blot were used to detect the intima-media thickness, collagen content, the change of collagen typeⅠ and CREG expression of arterial wall at different time after arterial injury. CREG was expressed in normal arteries. The expression of CREG mRNA and protein of the arterial wall was markedly down-regulated after injury of mouse carotid artery, and reached its lowest value on the third day after arterial injury, with close correlation to the process of vascular remodeling (increase in mRNA and protein level of collagen typeⅠ). CREG expression was gradually restored on the seventh day, and almost returned to normal levels on fourteenth day and twenty-eighth day after arterial injury. In contrast, injured arteries developed marked vascular remodeling after 7 days as manifested by increase in intima-media thickness, narrowing of the vascular lumen, collagen content as well as mRNA and protein level of collagen typeⅠ. There were negative relationships between CREG expression and vascular remodeling at the early time of artery injuries. The expression of CREG was decreased at beginning and then increased, but the degree of vascular remodeling was continued to exacerbate. These data strongly suggest that CREG is involved in the development of vascular remodeling after arterial injury, and that injury-induced CREG down-regulation may contribute to the progression of vascular remodeling.