Monodisperse microspheres of reconstituted silkworm cocoon silk were produced using a glass capillary-based microfluidic system and by identifying an appropriate solvent/nonsolvent fluid system. The microspheres can be produced to it range of different diameters depending oil the system flow rates and have it nearly homogeneous size distribution. The silk microspheres exhibit it unique core-shell architecture and have it largely beta-sheet structure, as measured by infrared spectroscopy, Mechanical characterization was performed with AFM nanoindentation and indicates that the microspheres are unexpectedly soft for a silk material. Because silk is well established Is biocompatible and biodegradable, we anticipate that these silk microspheres Could have particular utility in drug delivery and controlled release.