Massive pulmonary embolism (PE) is a cardiovascular emergency due to a substantial obstruction of the pulmonary vascular bed, resulting in rapid right heart failure with a potentially fatal outcome.We present the case of a 50-year-old woman with massive PE and recent trans-sphenoid surgery because of pituitary adenoma. An occluding embolus, arising from deep venous thrombosis of the lower limbs, was demonstrated in the right pulmonary artery with selective angiography and treated with selective loco-regional infusion of low-dose tenecteplase. To the best of our knowledge, this is the first case of selective administration of low-dose tenecteplase in the pulmonary artery with successful resolution of PE without the need for adjunctive interventional procedures.