Insulin, 3 IU/kg body weight, given intranasally in a hypoosmotic thermogelling system, containing EHEC, SDS, m-cresol and glycerol, is more efficient in lowering plasma glucose than insulin delivered in iso- and hyperosmotic gels. This has been shown for two osmotic agents, glycerol and creatinine. The effect is significantly different from a plain hypoosmotic insulin solution, which did not have any effect on the plasma glucose. This suggests that there is a synergistic effect of the hypoosmotic environment and the EHEC gel. However, both m-cresol and insulin participate in gel formation. Therefore, the insulin is partly associated with the gel matrix and not all of the insulin is available for absorption. An optimal gel system should be a thermosetting polymer solution with mucoadhesive properties, that rapidly releases the insulin content under hypoosmotic conditions.