Amegakaryocytic thrombocytopenia (AMT) is a rare cause of acquired thrombocytopenia. The pathogenesis and treatment of AMT is not clearly known. Here we demonstrate a 50-year-old man presented with the clinical manifestations of severe thrombocytopenia (7000 platelets/µl) with a marked decrease to absent of megakaryocytes in the bone marrow. The patient did not respond to intravenous immunoglobulin, cyclosporine or high dose prednisone. After the treatment with anti-CD20 antibody (Rituximab), the patient's clinical symptoms and platelet counts improved.