With the intention to modulate gene expression in vascular mural cells of remodeling vessels, we generated and characterized transgenic mouse lines with Cre recombinase under the control of the platelet‐derived growth factor receptor‐β promoter, referred to as Tg(Pdgfrb‐Cre)^35Vli. Transgenic mice were crossed with the Gt(ROSA)26Sor^tm1Sor strain and examined for Cre activation by β‐galactosidase activity, which was compared with endogenous Pdgfrb expression. In addition, Pdgfrb‐Cre mice were used to drive expression of a conditional myc‐tagged Cthrc1 transgene. There was good overlap of β‐galactosidase activity with endogenous Pdgfrb immunoreactivity. However, dedifferentiation of vascular mural cells induced by carotid artery ligation revealed a dramatic discrepancy between ROSA26 reporter activity and Pdgfrb promoter driven Cre dependent myc‐tagged Cthrc1 transgene expression. Our studies demonstrate the capability of the Pdgfrb‐Cre mouse to drive conditional transgene expression as a result of prior Cre‐mediated recombination in tissues known to express endogenous Pdgfrb. In addition, the study shows that ROSA26 promoter driven reporter mice are not suitable for lineage marking of smooth muscle in remodeling blood vessels. genesis 49:673–680, 2011. © 2011 Wiley‐Liss, Inc.