Wetting and dewetting phenomena are ubiquitous, but wetting transitions have been reported only in a few experimental systems. In this work, we present a wetting transition in a mesoscopic membrane compartment for the first time. A two-phase aqueous polymer solution was encapsulated in a giant vesicle (few tens of micrometers in size). The polymers used are poly(ethyleneglycol) (PEG) and dextran. By increasing the polymer concentration in the vesicle, the PEG-rich phase changed from complete wetting to partial wetting of the membrane.