Diabetes mellitus in patients with thalassemia major is caused by secondary hemochromatosis due to transfusional iron overload. This study is performed to study the prevalence of and risk factor for abnormal glucose tolerance in transfusion dependent β-thalassemic patient. A total of 54 thalassemic patients were examened and participated in an OGTT and compared to 28 healthy controls. Insulin secretion and insulin resistance were assessed by HOMA models. The prevalence of impaired glucose tolerance was 13% and that of diabetes was 11.1% and only one of diabetic patient presented with diabetic ketoacidosis. The risk factors for glucose intolerance in thalassemic patients were the blood transfusion interval, serum ferrtin concentration, and hepatitis C viral infection. Moreover patients with abnormal glucose toelrance showed moderate reduction of β-cell function together with the presence of insulin resistance. Furthermore 40.7% of the included patients had short stature and 88.9% suffered from delayed puberty. In conclusion: Patients with thalassemia major have significant insulin resistance which may be compensated for by an elevated circulating insulin level. Persistent insulin resistance together with progressive reduction in circulating insulin levels (due to progressive β-cell failure) may lead to glucose intolerance and diabetes in TM patients.