Acetic acid (AcOH) is a short-chain fatty acid (SCFA) that is produced as a result of colonic bacterial fermentation of dietary fiber. Dietary fiber has several beneficial metabolic effects, including the reduction of the postprandial glycemic response, lowering of plasma cholesterol and triglyceride concentrations, and reduction in fat storage [5]. Several reports have suggested that increased SCFA production in the bowel might, in part, account for some of these effects [5]. In addition to resulting from colonic bacterial fermentation of dietary fiber, AcOH is available through dietary sources, as it is widely consumed in meals. AcOH is the primary constituent of vinegar, being present at concentrations of 3–5 g/100 g. Vinegar, commonly used as a seasoning, also has been used traditionally as a folk medicine. Recently, the medicinal properties of oral administration of AcOH were confirmed. Consumption of AcOH was reported to be beneficial in the treatment of hypertension [6] and in enhancing glycogen repletion after fasting [7]. However, the effect of AcOH on type 2 diabetes is not well understood. A recent study suggested that acetate, in the form of neutralized AcOH, activated AMPK in rat hepatocytes [8]. Hepatic AMPK activation leads to suppression of gluconeogenesis and, subsequently, reduction in hyperglycemia [1] and [2]. Therefore, the central aim of the present study was to determine whether AcOH ameliorates type 2 diabetes by activating hepatic AMPK. Using diabetic KK-A(y) mice, we demonstrated that a diet supplemented with AcOH reduced hyperglycemia through the suppression of genes that regulate gluconeogenesis and lipogenesis. Such genes are in part regulated by AMPK