We report that (a) chronic blockade of the TLR4–MD2 complex lowers BP in diabetic animals; that (b) type 1 diabetes modulates the levels of MD2 expression in the aorta, but not TLR4, at least in the conditions evaluated in this study; and, that (c) acute inhibition of TLR4 or MD2 diminishes vascular contractility and reduces oxidative stress in the aorta of these animals. Here, LY96 is linked to type 1 diabetes mellitus.