Pioglitazone improves insulin sensitivity and glycemic control in patients with T2DM (4, 10-12), but the mechanism of action of TZDs is unclear (13, 14). Pioglitazone activates genes involved in lipid synthesis, causing a reduction in plasma free fatty acid (FFA) and triglycerides (15). TZDs decrease excessive triglyceride accumulation in liver (16), muscle (17), and visceral fat (11, 16, 18), with a redistribution of fat to subcutaneous adipose stores (14). TZDs also antagonize the metabolic effects of TNF-alpha (19-22). Because pioglitazone ameliorates insulin resistance, reverses the metabolic abnormalities that contribute to hepatic fat infiltration (increased plasma glucose, FFA, and triglyceride concentrations), and antagonizes the effects of TNF-alpha, it follows that pioglitazone may prove useful for the treatment of patients with NASH.