Poly(DL-lactide-co-glycolide) nanoparticles were prepared by the modified spontaneous emulsification solvent diffusion method. Polymer solution was prepared by two water-soluble organic solvents, such as ethanol and acetone. Because of its biocompatible nature, PEG-PPG diblock copolymer was used as surfactant and stabilizer. The influence of several preparative variables on the nanoparticle formation, such as type and concentration of stabilizing agent, stirring methods, water/oil phase ratio and polymer concentration were investigated in order to control and optimize the process. After preparation of nanoparticles, particle size and distribution were evaluated by the light scattering particle analyzer. As results, the particle size was 50-200 nm and dispersibility was monodisperse. It was found that the appropriate selections of binary solvent mixtures and polymeric concentrations in both organic and aqueous phases could provide a good yield and favorable physical properties of PLGA nanoparticles.