Transforming growth factor-beta (TGF-beta) signaling has been prominently implicated in the pathogenesis of vascular remodeling, especially the initiation and progression of flow-induced vascular remodeling. Smooth muscle cells (SMCs) are the principal resident cells in arterial wall and are critical for arterial remodeling. However, the role of TGF-beta signaling in SMC for flow-induced vascular remodeling remains unknown. Therefore, the goal of our study was to determine the effect of TGF-beta pathway in SMC for vascular remodeling, by using a genetical smooth muscle-specific (SM-specific) TGF-beta type II receptor (Tgfbr2) deletion mice model. Mice deficient in the expression of Tgfbr2 (MyhCre.Tgfbr(f/f)) and their corresponding wild-type background mice (MyhCre.Tgfbr2(WT/WT)) underwent partial ligation of left common carotid artery for 1, 2, or 4 weeks. Then the carotid arteries were harvested and indicated that the disruption of Tgfbr2 in SMC provided prominent inhibition of vascular remodeling. And the thickening of carotid media, proliferation of SMC, infiltration of macrophage, and expression of matrix metalloproteinase (MMP) were all significantly attenuated in Tgfbr2 disruption mice. Our study demonstrated, for the first time, that the TGF-beta signaling in SMC plays an essential role in flow-induced vascular remodeling and disruption can prevent this process. (C) 2014 Elsevier Inc. All rights reserved.