Herbal medicines, especially plant-derived extracts, have been used to treat Type 2 diabetes mellitus (T2DM) for many centuries, and offer the potential of cheap and readily available alternatives to conventional pharmaceuticals in developing countries. Extracts ofGymnema sylvestre(GS) have anti-diabetic activities and have been used as a folk medicine in India for centuries. We have investigated the effects of a novel high molecular weight GS extract termed OSA® on glucose tolerance in insulin-resistant ob/ob mice, and on insulin secretion and synthesis by isolated mouse islets. Single administration of OSA® (500 mg/kg) to ob/ob mice 30 min before an intraperitoneal glucose load improved their abnormal glucose tolerance.In vitrostudies indicated that OSA® (0.25 mg/ml) initiated rapid and reversible increases in insulin secretion from isolated mouse islets at substimulatory (2 mM) and stimulatory (20 mM) glucose concentrations. In addition, prolonged treatment (24–48 h) of mouse islets with OSA® elevated the expression of preproinsulin mRNA and maintained the total insulin content of mouse islets in the presence of stimulated insulin secretion. These effects of OSA® are consistent with its potential use as a therapy for the hyperglycemia associated with obesity-related T2DM. Copyright © 2012 John Wiley & Sons, Ltd.