The ex vivo permeation of lidocaine hydrochloride, a model drug, was studied in two different regions of the oral mucosa: pig palate (keratinized) and cheek (non-keratinized). The enhancing effect of a series of sucrose fatty acid esters (nonionic surfactants), which have the advantage of reduced irritation potential relative to other enhancers, was investigated. Among the sucrose esters tested, an increase in the passage of lidocaine through buccal and palatal mucosae was observed only for sucrose laurate (L-1695) (enhancement ratio (ER) ∼22 for buccal and ∼14 for palatal mucosa). The other sucrose esters (S-1670, O-1570 and P-1670), did not show any promoting effect. The type of fatty acid sucrose ester, was found to be a key factor for promoting the absorption of lidocaine. The contribution of sucrose esters was compared with that of other enhancers, such as ethanol, oleic acid and Transcutol®. A significant enhancing effect was observed with oleic acid/hydroalcoholic solution, for both buccal and palatal mucosa (ER ∼13 and ∼61, respectively). However, there was no promotion when the hydroalcoholic solution was applied in the absence of oleic acid. A synergic effect between oleic acid and ethanol is very probable. A slight promoting effect was obtained when Transcutol/water (50:50) was used as the vehicle.