The present invention relates to a composition comprising a Ninjurin1 expression or activity inhibitor for the prevention and treatment of inflammatory disease. Ninjurin1 protein is specifically expressed in macrophages around blood vessels, increases cell-cell adhesion and cell-matrix adhesion, increases expressions of Wnt7b (Wingless-type MMTV integration site family, member 7B) and Ang2 (angiopoietin-2), but reduces expression of Ang1 to induce apoptosis of vascular endothelial cells. In addition, Ninjurin1 protein is up-regulated when inflammation is induced and induces iNOS expression as well as increased NO generation. Therefore, the Ninjurin1 protein expression or activation inhibitor can be effectively used as an active ingredient of a composition for the prevention and treatment of inflammatory disease.