To clarify whether prostaglandin synthesis is involved in the regulation of insulin release from isolated rat islets, we performed three different experiments. The direct effects of prostaglandin E_1 and prostacyclin on insulin release were investigated. Neither prostaglandin had any effect in the presence of low and high concentrations of glucose. Indomethacin, aspirin^<[○!R]> (acetylsalicylic acid) and flurbiprofen, inhibitors of cyclooxygenase, did not have a significant effect on insulin release evoked by glucose. Exogenous phospholipase A_2 purified from bee venom and melittin stimulated insulin release. A potent and selective inhibitor of phospholipase A_2,mepacrine, inhibited glucose-induced insulin release. The present work indicates that 1) cyclooxygenase does not participate early release of insulin from islet 2) activation of phospholipase A_2 might be involved in insulin stimulus-secretion coupling.