Aim:The effects of pioglitazone hydrochloride monotherapy on abnormal lipid control were evaluated in Japanese patients with type 2 diabetes mellitus, comparing with glibenclamide monotherapy. Methods: Patients were randomly assigned to receive, once daily, pioglitazone hydrochloride, at 15 mg or 30 mg (n 46), or glibenclamide, at 1.25 mg or 2.5 mg (n 46). The 24-week study included patients with type 2 diabetes having high levels of triglyceride (TG). Results: Pioglitazone hydrochloride produced beneficial effects on dyslipidemia in patients with type 2 diabetes, compared with the baseline and the glibenclamide group, as demonstrated by increases in high-density lipoprotein cholesterol (HDL-C) levels and low-density lipoprotein cholesterol (LDL) particle size, a fall in TG levels, and an increased ratio of visceral to subcutaneous fat volumes (V/S). Pioglitazone hydrochloride reduced fasting serum insulin levels, with low fasting plasma glucose (FPG) and glycohemoglobin levels, compared to the baseline, suggesting an improvement of insulin resistance. Conclusion: As expected, glibenclamide reduced FPG levels through increased insulin secretion. Pioglitazone hydrochloride and glibenclamide were well tolerated. Pioglitazone hydrochloride improved dyslipidemia related to insulin resistance, whereas glibenclamide enhanced insulin secretion, with only a minor effect on lipid control, in Japanese patients with type 2 diabetes.