A series of alkylglycosides with various alkyl chain lengths and carbohydrate residues were tested for their ability to enhance systemic absorption of insulin after topical ocular delivery in anesthetized rats. Several reagents, including tetradecyl-, tridecyl- and dodecylmaltoside and dodecylsucrose, were potent stimulators of insulin absorption when used at concentrations as low as 0.125%. Other alkylglycosides such as decylsucrose, decylmaltoside, nonylglucoside, octylmaltoside, heptylglucoside and hexylglucoside were less potent or ineffective as absorption-enhancing reagents. By comparison, the bile salt sodium glycocholate was effective only when used at concentrations of 0.5% or greater. All of the reagents were effective only when used at concentrations above their critical micelle concentration and the most hydrophobic alkylglycoside reagents were the most efficacious at promoting systemic insulin absorption. The possible utilization of eyedrops containing insulin plus an absorption-enhancing alkylglycoside reagent in humans is discussed.