Insulin treatment is associated with two important and frequent side effects: hypoglycemia and weight gain. Weight gain is in contradiction with the physiological central effect of insulin which leads to decreased food intake like leptin. However, decreased urinary caloric loss due to better glycemic control, prevention and correction of hypoglycemia, the anabolic effect of insulin and the possible central resistance to insulin explain the observed weight gain. Insulin is often necessary when oral antidiabetic treatment fails; the physician and the patient need to remain alert to minimize the side effects through adequate insulin regimen and life style.