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Serum sTNFRI, sTNFRII and IL-6 levels may indicate IVIG response in KD.Sustained elevation of serum sTNFR II level was linked to the CALs development.Sustained elevation of sTNFR II ratio was also linked to the CALs development.Serum sTNFRII level and sTNFRII/I may indicate the development of CALs in KD.To investigate the clinical significance of serum soluble tumor necrosis factor receptor (sTNFR) II level and sTNFR II/I ratio as indicators of the development of coronary artery lesions (CALs) in Kawasaki disease (KD), we measured levels of serum sTNFR I and II, interleukin (IL)-6, IL-18, and neopterin in 63 patients with KD, including nine patients with CALs and 20 healthy controls. At the time of diagnosis of KD before intravenous immunoglobulin (IVIG) treatment, serum sTNFR I and II levels were found to be significantly higher in non-responders to IVIG treatment than in responders. On the contrary, serum sTNFR II levels and sTNFR II/I ratio were significantly higher in patients with KD having CALs than in those without CALs. Longitudinal observation in a patient with KD who is unresponsive to IVIG revealed sustained elevation of serum sTNFR II level, and elevated sTNFR II/I ratio was linked to the CALs development. Increase in serum sTNFR II level and elevated sTNFR II/I ratio may be promising indicators of the development of CALs in KD.