Objective: To investigated the effects and the mechanism of death domain-associated protein (DAXX) on vascular stenosis and smooth muscle cells proliferation in the balloon-injured rat carotid artery. Methods: Thirty-two male SD rats were divided into 4 groups: a sham-surgery group, a surgery group, a blank-transfected group, and a transfected group. The gross artery in the sham-surgery group were free, in the surgery group the carotid artery were injured by using balloon, based on the above the blank-transfected group and the transfected group was transfected DAXX plasmid or DAXX blank plasmid by using topical liposome. Every rat’s carotid artery was exposed. We collected carotid artery segments of each groups at 7 and 14 days. HE was used to assess the degree of vascular stenosis. Immunohistochemistry and PCR were performed to detect the expression of DAXX and Jun N-terminal kinase ( JNK). Results: In the surgery group, smooth muscle cells significantly increased, vessels wall thickened, luminal narrow at 7 days and 14 days. While in the transfected groups luminal were relatively smoother, smooth muscle cells were less, the intimal/medical area ratio were lower when compared with the surgery group (P<0.01). The expression levels of mRNA, protein of DAXX and JNK in the surgery group were higher than those in the sham-surgery group and less than those in the transfected group (P<0.01). Conclusion: Topical high expression of DAXX may inhibit the proliferation of smooth muscle cells in mice carotid after the balloon-injured surgery and reduce the vascular stenosis, the mechanism may be related with JNK singaling pathway.