Here, we showed that (a) blockade of TLR4 lowers BP in diabetic animals; that (b) type 1 diabetes differentially modulates the TLR4–MD2 complex in the aorta; and, that (c) the TLR4–MD2 complex contributes to vascular dysfunction in the aorta of STZ-induced diabetic animals. This evidence concerns the gene LY96 and type 1 diabetes mellitus.