A 44-year-old man with neurofibromatosis suffered from severe diarrhea and progressive hypoproteinemia. Enteric protein loss was confirmed by an alpha 1-antitrypsin clearance test. An x-ray study showed irregular mucosa in the distal segment of the ileum. Protein loss has subsided after ileocecal resection. Laparotomy and radiological examinations failed to demonstrate neurofibroma or other tumors in the abdomen. The resected ileum revealed marked edema of the wall and a pseudomembranous enteritis-like appearance in the luminal surface. Microscopically, lymphatic vessels in the intestinal wall were dilated. Marked thickening of the intima with spindle cell proliferation was observed in the mesenteric arteries and veins. This finding is consistent with vascular changes in neurofibromatosis. These vascular changes in the mesentery due to neurofibromatosis may cause protein-losing enteropathy by altering the hemodynamic state and microvascular permeability in the intestine.