BACKGROUND Portal vein thrombosis in adults is usually related to cirrhosis. There are several possible therapies. including anticoagulation, transjugular intrahepatic portosystemic shunt, balloon dilatation, local and systemic fibrinolytics agents. Hypercoagulable states are also reported in association with this disease entity. Eosinophilia may activate platelets and promote thrombosis due to proteins contained in intracytoplasmic granules, such as eosinophil cationic protein and major basic protein. There is only one paper in the medical literature linking eosinophilia and portal vein thrombosis. METHODS We present here the case of a middle-age woman with idiopathic eosinophilia and acute portal vein thrombosis with massive venous thrombosis, involving the mesenteric, splenic, inferior cava, iliac and femoral veins, successfully treated with systemic streptokinase. CONCLUSIONS Acute portal vein thrombosis with associated mesenteric and splenic vein thrombosis is a potentially lethal coagulation disorder that can be treated successfully with systemic streptokinase.