In this work, the mechanism analysis of Poly(DL-lactic acid) (PLA) particles formation is investigated by dissipative particle dynamics (DPD) simulations. The polymer PLA is usually as a carrier at the drug deliver system (DDS), first, the mechanism analysis of PLA particles formation was preceded on the basis of the blank PLA particles. At the same time, the formation of PLA particles for drug delivery systems has been investigated. The results of DPD simulations indicate that the formation of PLA particles with drug or not, consists of three steps: (1) aggregation-individual PLA chains got aggregated with each other in solution; (2) formation and disruption of PLA particles; (3) solidification of PLA particles. At the same time, the effects of PLA, drug content on the aggregation morphology are investigated, which indicates the PLA particles with drug or not aggregated and formed is spherical particles, drug molecules are amorphously and homogeneously distributed inside the PLA matrix, the size of PLA particles increases with increasing the initial PLA content and drug content in the solution. The content of DMF is gotten when PLA chains and drug molecules begin to aggregate and form the particles. These could be used to guide the experimental preparation of PLA blank particles and DDS with desired properties. (C) 2010 Wiley Periodicals, Inc. J Appl Polym Sci 119: 3273-3281, 2011