This study investigates the effect of some formulation variables on particulate characteristics of poly (DL-lactide-co-glycolide) (PLGA) copolymer nanoparticles by applying 2³ factorial design and response surface methodology (RSM). Nanoparticles were prepared by solvent displacement technique. Initially, appropriate formulation factors for elaboration of polymeric particles were selected by screening. A 2³ full factorial design was employed to evaluate the influence of three formulation variables, polymer concentration (X₁), dispersant concentration (X₂) and phase volume ratio (X₃) on the percentage of total particles at submicron range (Y₁), mean diameter (Y₂) and specific surface area (Y₃) as particle characteristics. The results showed that all the three variables had significant influence on mean diameter of particles and amount of particles at submicron range. Simultaneous change of polymer concentration and dispersant concentration had significant effect on specific surface area of particles. Span value as an index of polydispersity indicated uniformity in particle size distribution.