SCOPE: Quercetin is a typical flavonol with atheroprotective effects, but the effect of quercetin on dendritic cell (DC) maturation in relation to atherosclerosis has not yet been clearly defined. Thus, we investigated whether quercetin can inhibit DC maturation and evaluated its potential value in atherosclerosis progression in ApoE(-/-) mice. METHODS AND RESULTS: Quercetin consumption inhibited DC activation, inflammatory response and suppressed the progression of atherosclerosis in ApoE(-/-) mice. Subsequently, quercetin treatment inhibited the phenotypic and functional maturation of DCs, as evidenced not only by downregulation of CD80, CD86, MHC-II, IL-6 and IL-12 but also by a reduction in the ability to stimulate T cell allogeneic proliferation. Finally, an in vitro study demonstrated that quercetin inhibited DC maturation via upregulation of Dabs, which then downregulated the Src/PI3K/Akt-NF-κB-inflammatory pathways. CONCLUSIONS: Our data indicate that quercetin attenuates atherosclerosis progression by regulating DC activation via Dab2 protein expression.