Bilayers prepared from sorbitan fatty acid esters (Span) have been frequently used for delivery of drugs including flavonoids. We applied molecular dynamics simulation to characterize the structure of a sorbitan monostearate (Span 60) bilayer in complex with three representative flavones, a subclass of flavonoids. At a low concentration, unsubstituted flavone, the most hydrophobic member, was able to flip over and cross the bilayer with a large diffusion coefficient. At a high concentration, it was accumulated at the bilayer center resulting in a phase separation.