The preparation of highly crosslinked polymer microspheres through the polymerization reaction in an alcohol-water solution without any stabilizer is still a difficult task. Here, we first reported a facile preparation of monodispersed highly-crosslinked microspheres through the polymerization of ethyleneglycol dimethacrylate (EGDMA) in an alcohol-water solution in the presence of a small amount of hydrophilic comonomer with a high reactivity ratio in a sealed autoclave at above the boiling point of the solvent, which can be considered as a solvothermal precipitation polymerization process. The formation mechanism of the poly(ethyleneglycol dimethacrylate) (PEGDMA)-based microspheres involving an initial nucleation process and the grow process of the microspheres was proposed and confirmed by the composition and distribution of the hydrophilic comonomer in the oligomers and microspheres, which were analyzed by H-1 and C-13 CP-MAS solid NMR spectra, elemental mapping, and XPS. This work opens a new economic and environmental-friendly way to prepare highly-crosslinked functional PEGDMA-based microspheres. (C) 2015 Elsevier Ltd. All rights reserved.