The present study investigated the effect of resveratrol on the electrophysiology and insulin secretion of pancreatic beta cells, and examined resveratrol-induced alterations in insulin levels and plasma glucose of normal and streptozotocin-induced diabetic rats. Whole-cell voltage clamp study in the MIN6 cell, a mouse beta cell line, revealed that resveratrol significantly inhibited ATP-sensitive K(+) current at 3 micromol/l, and voltage-gated K(+) currents at 30 micromol/l. Ca(2+)-activated K(+) current was activated by resveratrol at 100 micromol/l. In MIN6 cells stained with membrane potential dye DiBAC(4)(5), resveratrol markedly depolarized membrane potential at the concentrations of 3-100 micromol/l. Insulin secretion was increased in the presence of resveratrol in MIN6, Hit-T15, and RIN-m5F cells. Resveratrol (3 mg/kg, i.p.) increased insulin secretion associated with a lowering in plasma glucose in normal rats, but not in streptozotocin-diabetic rats within the initial 60 min. In conclusion, resveratrol can act as an insulin-secretagogue through I(KATP) and I(KV) inhibition which can contribute to plasma glucose lowering effect in normal rats.