The extracellular matrix (ECM) builds up a heterogeneous network of macromolecules that surrounds the cells and provides support to tissues. It was generally assumed that the ECM is primarily of importance for the formation and maintenance of organs. In the meanwhile it has become clear that molecules of the ECM can also bind to cell surface receptors and activate intracellular signaling pathways. Several ECM molecules were identified to affect the vascular system by regulating endothelial cell growth and angiogenesis. While the role of ECM peptides in angiogenesis and neo-vascularization is well established their impact on vascular tone regulation is less clear. Therefore, we investigated the vasomodulatory effect of different ECM peptides. Endostatin, a cleavage protein of collagen XVIII, was found to induce an endothelium-dependent vasorelaxation while a nonapeptide of the laminin beta1 chain evoked vasoconstriction in systemic arteries via depolarization of smooth muscle cells. RGD-peptides which provide adhesion of different matrix molecules to cells induced vasodilatory effects in both, systemic and pulmonary arteries. Our experimental data reveal novel mechanisms involved in the development of general and/or local changes of vascular tone during tissue remodeling.