Extracorporeal membrane oxygenation (ECMO), can be a life-saving intervention, but is associated with high complication rates. ECMO induces systemic inflammation and endothelial hyperpermeability, thereby causing tissue edema, microcirculatory perfusion disturbances and organ failure. This study investigated whether inhibition of vascular endothelial protein tyrosine phosphatase (VE-PTP), a regulator of endothelial permeability, reduces extracorporeal circulation (ECC)-induced microvascular dysfunction in rats.