The topic of this paper is the study of the drug release from a drug-loaded microemulsion by reverting to a new mathematical model overcoming some drawbacks of previously proposed models. In particular, attention is focused on the mathematical expression of the drug fluxes existing between the oil and water phases during drug release. Indeed, not only the drug release kinetics, but also the drug oil-water partition coefficient strongly depend on these fluxes. Two microemulsion are considered: the first is composed by water, Tween80 as surfactant, and Triacetin as oil phase, while the second is composed by water, Tween80 as surfactant, and a Triacetin-benzylic alcohol mixture (1 : 1) as oil phase. Both of them are loaded by Nimesulide, an oil-soluble drug of considerable industrial relevance. The drug release is performed by resorting to a permeation experiment (Franz cells apparatus) as it demonstrated to be the most reliable methodology. The good agreement between the experimental permeation data and the model best-fitting ensures that the most important phenomena ruling this kind of drug release were properly accounted for by the new proposed model. Copyright 2000 Academic Press.