To investigate the factors affecting weight gain following 5-year treatment with pioglitazone (PIO), 1,184 type 2 diabetic patients were analyzed retrospectively. PIO administration caused a mean 2.8 kg in weight gain. The mean body weight increased up to one year and was maintained at a stable value for up to five years. The degree of weight gain in females was greater than that observed in males. The coadministration of sulfonylureas increased the degree of weight gain, whereas the coadministration of α-glucosidase inhibitors inhibited increased weight gain. A significant correlation was found between the degree of weight gain and the HbA1c level and body mass index before the administration of PIO. Although the administration of PIO caused significant weight gain, three risk factors of atherosclerosis (HbA1c, HDL-cholesterol and blood pressure) were observed to improve.