Ginsenoside Rg1 (Rg1), one of the main active components of Panax ginseng, has been demonstrated to inhibit proliferation of vascular smooth muscle cells (VSMCs) induced by tumor necrosis factor-α in vitro.The present study is aimed to examine the possible effects of Rg1 on vascular neointimal hyperplasia in balloon-injured carotid artery of rats in vivo.The animal model was established by rubbing the endothelia with a balloon catheter in the common carotid artery (CCA) of male Sprague Dauley rats.Then the rats were intraperitoneally injected with distilled water in model group and sham operation control, or with Rg1 4 mg· kg-1 · d-1 , 8 mg · kg-1 ·d-1 and 16 mg·kg-1 ·d-1 in other balloon injured groups.After consecutive 14 d, the vascular intimal hyperplasia was evidenced by histopathological changes of the CCA and the protein expression of proliferating cell nuclear antigen (PCNA) , a marker of the proliferation in VSMCs, and the phosphorylated extracellular signal-regulated kinase2 (pERK2) as well as mitogen-activated protein kinase phosphatase-1 (MKP-1) were examined by immunohistochemistry; the expressions of proto-oncogene (c-fos) , ERK2 and SM α-actin mRNA were analyzed by Real-Time RT-PCR.The results demonstrated that Rgl administration could significantly ameliorate the histopathology of CCA and decrease the protein expression of PCNA induced by endothelia rubbing; and Rgl medication also significantly decreased the expressions of p-ERK2 protein, ERK2 and c-fos mRNA in vessel wall, but up-regulated the MKP-1 expression, which was reported to inactivate mitogen-activated protein kinase pathway.Furthermore, Rg1 could elevate the decreased SM α-actin mRNA expression induced by balloon injury.It is concluded that Rg1 can suppress the vascular neointimal hyperplasia induced by balloon injury, the mechanism may be involved in the inhibition on ERK2 signaling, and related, at least partly, to the increase in MKP-1 expression.