Lymphangiomatosis is a rare disorder believed to result from a developmental malformation of the lymphatic system. Lymphangiomatosis involves bone, soft tissues, and viscera in a diffuse fashion. We describe an unusual case of splenic lymphangiomatosis that was accompanied by remarkable inflammatory signs. A 38-year-old Japanese woman was admitted to our hospital because of gross splenomegaly. She presented with fatigue, anemia, elevated serum C-reactive protein and polyclonal hypergammaglobulinemia. Her serum concentration of interleukin-6 (IL-6) was also elevated. She was born with lymphangiomatosis in the right leg, which was partially resected during infancy. Because of the risk of traumatic rupture, a total splenectomy was performed two weeks after admission. During postoperative follow-up examinations the patient's inflammatory signs and her serum IL-6 level returned quickly to normal. This could have been caused by a large release of IL-6 from the spleen. We confirmed by immunohistochemistry that IL-6 was produced within the spleen. Our findings indicate a strong association between splenic lymphangiomatosis and IL-6 production.