Background: Kawasaki disease (KD) is a systemic vasculitis with cardiac and noncardiac complications. Anti-endothelial cell antibodies (AECA), especially IgM class, were found in the sera of many patients with KD. AECA may increase endothelial cell intercellular adhesion molecule-1(ICAM-1) expression, and may be important in the development of KD. The aim of this study was to investigate the pathogenic role of AECA in KD. Materials and Methods: Sera IgM-AECA and plasma concentrations of TNF-慣 were investigated in 22 KD patients with ELISA method. Human coronary artery endothelial cells (HCAEC) were incubated with acute or convalescent phase sera. Expression of ICAM-1 was assessed by fluorescence -activated cell sorting (FACS). IgM fractions were purified by gel filtration from the AECA-positive sera. Their ability to induce ICAM-1 expression were evaluated by ELISA method. To determine which MAPK signaling pathway is required for AECA induced ICAM-1 expression, we have utilized the protein kinase inhibitor PD98059 (a specific inhibitor of MER1/2), dimethylaminopurine (DMAP, a specific inhibitor of JNK), SB203580 (a specific inhibitor of p38), and parthenolide (specific NF-캡B inhibitor). Results: IgM-AECA were presented in 14 out of 22 (64%) acute sera, and 2 out of 22 (9%) convalescent sera. Two patients with significantly high AECA levels developed coronary aneurysms. The mean concentration of plasma TNF-慣 in acute-phase was 3.4짹1.6 pg/ml, which was lower than the concentration of TNF-慣 needed to upregulation of ICAM-1 expression (10 pg/ml). ICAM-1 expression by HCAEC incubated with acute sera (117.1짹46.7) or AECA-positive sera (143.3짹37.5) were significantly higher than incubated with convalescent sera (88.9짹14.4) or AECA-negative sera (71.2짹11.8) (p<0.05). IgM-AECA from KD patients induced ICAM-1 expression on HCAEC. The upregulation of ICAM-1 expression was markedly inhibited by DMAP and SB203580. Conclusions: AECA from patients with KD were able to active endothelial cells by upregulation of adhesion molecule expression, possibly, via activation of JNK and p38 MAPK signal transduction pathways. These findings suggest the pathogenic role of AECA in the development of KD.