A novel type of highly uniform polymer microspheres, poly(urea-siloxane) (PUSs) was prepared through the precipitation polymerization of 1,3-bis(3-aminopropyl)-1,1,3,3-tetramethyldisiloxane (APTMDS) with isophorone diisocyanate (IPDI) in H2O-acetone mixed solvent. No additives such as surfactant and initiator were used. The effects of monomer ratios, H2O/acetone ratios, and monomer concentrations on the yields and morphologies of the PUSs were investigated. Results indicated that PUSs sizes can be regulated from 2.14 µm to 7.11 µm by varying monomer ratios, monomer concentrations and H2O/acetone ratios. Hydrogen bonds between polyurea units, polyurea and APTMDS moieties which were identified as the main effects of the products, endowed the materials with good elasticity. The structures and morphologies of the materials were characterized by FT-IR, NMR, and SEM, and the thermal properties were characterized by TGA and DSC analyses.