Background: Hemochromatosis is an inherited or secondary disorder caused by excessive iron storage leading to liver cirrhosis, cardiac dysfunction, hypothyroidism, diabetes and hypogonadism. In this study, we reports 2 cases of diabetes mellitus in patients with severe aplastic anemia following multiple transfusions. Case: Subject 1, 15-year-old male, was diagnosed with severe aplastic anemia and was treated with anti-thymocyte globulin and cyclosporine. He received multiple red blood cell transfusion with a total volume of 223 units before he got autologous peripheral blood stem cell transplantation at the age of 22 years. At age 21 years, hyperglycemia (serum glucose 358 mg/dL) was found on routine laboratory tests with high body mass index (36.5 kg/m2), hemoglobin A1c (9.7%), and serum ferritin (12,910 ng/mL; normal 20¬320 ng/mL). The 24-hour urine C-peptide level was normal with negative GAD-antibody. Since then, metformin and iron-chelating agent were administered. However, intensive insulin regimen was necessitated 2 years after the onset of diabetes. Subject 2 was diagnosed with severe aplastic anemia at age 2 years and received multiple red blood cell transfusions until she got haplo-identical peripheral blood stem cell transplantation at age 13 years. At age 11 years, she developed insulin-dependent diabetes mellitus caused by hemochromatosis with high serum ferritin level (12,559.8 ng/mL). She is currently 16 years old and has been under treatment with multiple daily insulin injections and estrogen/progesterone replacement therapy because of hypogonadotropic hypogonadism. Conclusions: This study reports two patients of diabetes mellitus by secondary hemochromatosis caused by multiple blood transfusions for severe aplastic anemia. Both loss of insulin secretory capacity and insulin resistance play a role in the pathogenesis of diabetes mellitus in hemochromatosis.