Giant vesicles were efficiently produced by squeezing a lipid (l-α-phosphatidylcholine from egg yolk)-coated marshmallow-like flexible macroporous silicone monolith in a buffer. The mean diameter of the obtained vesicles was 2 μm, showing a wide distribution, up to tens of micrometers, which was similar to that of vesicles formed by a natural swelling method. It was possible to prepare vesicle dispersions on a scale from several microliters to several hundred milliliters. A protein synthesis system (PURE system) contained in vesicles prepared using this method functioned effectively. Our absorbing-squeezing method is expected to help in studies that use giant vesicles such as artificial cells and drug delivery systems.