We investigated the effects of low-dose pioglitazone (7.5mg/day) on serum high molecular weight (HMW) adiponectin and fluid retention (estimated from hematocrit) in 14 male and 16 female patients with type 2 diabetes. All of them were being treated with sulfonylureas and had poor glycemic control. Patients were given 7.5 mg/day of pioglitazone and were followed for 12 weeks at monthly intervals. In all 30 patients, HbA1c was significantly decreased after 12 weeks of treatment with pioglitazone (8.2+/-0.7% vs. 7.4+/-0.8%, P<0.0001). Serum HMW adiponectin increased markedly from 5.2 (2.4, 8.6) microg/ml at baseline to 9.8 (4.1, 12.6) microg/ml at the end of pioglitazone treatment (P<0.0001). When the changes were evaluated separately for each sex, diabetic men showed no increase of body weight or BMI after treatment, while HbA1c decreased significantly, and did Hct. Serum HMW adiponectin increased significantly after treatment. In diabetic women, neither body weight nor BMI increased after treatment with pioglitazone, as was the case for the men. HbA1c decreased significantly, and did Hct. Serum HMW adiponectin increased significantly after treatment. In conclusion, low-dose pioglitazone therapy could significantly improved glycemic control and markedly increased serum HMW adiponectin in both male and female Japanese patients with type 2 diabetes.