Endocan is increased in the serum and lung of MCT-induced PAH rats. Endocan knockdown significantly improves right ventricular systolic pressure in MCT-induced PAH rats. Endocan knockdown inhibits the permeability increase and adhesion molecules secretion in RPMECs induced by TNF-α in vitro. Endocan knockdown inhibits the MAPK activation induced by TNF-α in vitro.