Nondiabetic rats were anesthetized with xylazine/ketamine to induce hyperglycemia and systemic insulin absorption from eyedrops formulated with dodecylmaltoside was quantitated by both a decrease in serum levels of D-glucose and an increase in immunoreactive insulin levels. When insulin eyedrop administration was delayed until 60 minutes after the administration of eyedrops containing 0.25% dodecylmaltoside, the enhanced systemic absorption of insulin was maintained, suggesting that dodecylmaltoside had an effect directly on the permeability of the nasal sinus epithelium. When glucagon was formulated in eyedrops or nosedrops containing dodecylmaltoside, systemic absorption of glucagon could be measured in the form of an increase in the serum D-glucose concentration following nasal application, but not after ocular application. Eyedrops containing insulin plus 0.125% dodecylmaltoside were administered to a diabetic dog; a dose of 20 units of regular insulin caused a modest decrease in serum D-glucose concentration and a concomitant increase in serum immunoreactive insulin content. These results provide evidence that peptide drugs such as insulin can be formulated in eyedrops with low concentrations of dodecylmaltoside, a mild nonionic surfactant.