Kawasaki disease is characterized by granulomatous inflammation of coronary arteries. We previously reported that a synthetic Nod1 ligand FK565 induced coronary arteritis in mice similar to that of Kawasaki disease. However, the molecular mechanism underlying this site-specific vasculitis has remained elusive. We found that CD11c+ MHC class II+ cells were accumulated in heart of FK565-treated mice prior to arteritis development, which was abolished in Nod1-/- mice. In vivo depletion of mononuclear phagocytes or CD11c+ cells prevented the arteritis, whereas elimination of T cells, B cells, NK cells, and neutrophils did not alter the pathology. Morphological features and gene expression signature of the cardiac CD11c+ MHC class II+ cells suggested that this population was closely related to macrophages. Notably, various inflammatory cytokines, chemokines, lysosomes and MMPs were expressed in these cardiac CD11c+ macrophages, suggesting that this population contributed to tissue destruction. Next, we determined whether Nod1 in hematopoietic cells or non-hematopoietic cells were important for this arteritis. Bone marrow chimera mice using WT and Nod1-/- mice indicated that Nod1 in non-hematopoietic host cells, rather than in hematopoietic cells, was important for the accumulation of the cardiac CD11c+ macrophages and arteritis development. Among non-hamatopoietic cells, cardiac endothelial cells abundantly produced chemokines in response to FK565. In this respect, CCR2-deficient mice exhibited decreased cardiac CD11c+ macrophages and compromised inflammation. These results suggested that Nod1 activation in endothelial cells triggers accumulation of cardiac CD11c+ macrophages, which is a prerequisite for the development of coronary arteritis.