AIM To investigate the hypoglycemic effect of buccally delivered insulin solution (INS SOL) in normal rats. METHODS The hypoglycemic response was examined after buccal delivery of INS SOL co administered with various absorption enhancers. The pharmacological bioavailability (PA) was used to evaluate the absorption enhancement of INS SOL from the buccal cavity under various conditions compared with subcutaneous injection. RESULTS In the absence of enhancers, the PA was low(6 8%) after buccal delivery of INS SOL. However, the concomitant administration of sodium lauryl phosphate, sodium deoxycholate, Brij78 as well as lecithin appeared to be more effective in increasing the hypoglycemic effects of insulin. INS SOL (5 ??kg -1 ) containing 5% Brij 78 had the highest PA of 33%. CONCLUSION The use of proper absorption enhancers is useful for improving the buccal absorption of insulin.