The incidence of type 2 diabetes and metabolic disease is rapidly increasing, but effective therapies for their prevention and treatment have been poorly tolerated or minimally effective. In this study, chronic administration of kudzu root extract (8 months, 0.2%, w/w, in diet) decreased baseline fasting plasma glucose (183 ± 14 vs. 148 ± 11 mg/dl) and improved glucose and insulin tolerance in C57BL/6J ob/ob mice (1.67 ± 0.17 ng/ml [kudzu treated] vs. 2.35 ± 0.63 ng/ml [control]), but such treatment did not alter these parameters in lean control mice. Among the mice on the kudzu supplementation, plasma levels of isoflavone metabolites were significantly higher in ob/ob versus lean control mice, and unmetabolized puerarin (11.50 ± 5.63 ng/g) was found in adipose tissue only in the treated mice. Together, these data demonstrate that a puerarin containing kudzu diet improves glucose and insulin responsiveness in ob/ob mice, suggesting that puerarin may be a beneficial adjuvant for treating metabolic disease. © 2012 Elsevier GmbH.