Objectives: An outcome of the Fontan procedure has been improved recently, however not a few patients have failure of the Fontan circulation because of high pulmonary vascular resistance. Endothelin-1 (ET-1) is one of the most important vasoconstrictive substances, but there are only a few studies focused on ET-1 and especially on its receptors after the Fontan procedure. The aim of this study is to clarify the expression levels of ET-1 and endothelin receptor type A (ETAR) and type B (ETBR) in the pulmonary arteries of patients with failed Fontan circulation. Methods: We retrospectively analyzed ten autopsy lung tissues from the patients died after the Fontan procedure (group F), and compared to four normal lung tissues without cardiovascular disease (group N). We evaluated expression levels of ET-1, ETAR and ETBR in their pulmonary arteries using immunohistochemistry and quantitative real-time PCR. Results: The distal pulmonary arteries in group F displayed intimal and medial hypertrophy with increased wall thickness (p < 0.05 vs Group N). The expressions of ET-1, ETAR and ETBR in group F was significantly increased, and mRNA expression of ET-1 was also increased (p < 0.05 vs Group N). Conclusion: The pulmonary arteries of patients with failed Fontan circulation showed significant medial hypertrophy, and the expressions of ET-1, ETAR and ETBR were significantly increased. High ET-1 and its receptors expression in the small pulmonary arteries might deteriorate Fontan circulation by elevating pulmonary artery pressure and promoting vascular remodeling with medial hypertrophy.