A combined emulsion/polymer cross-linking/solvent evaporation technique was used to prepare magnetic chitosan microspheres (MCM) containing the anticancer drug, oxantrazole. A central composite experimental design was used to simultaneously evaluate a variety of formulation factors on a number of response variables, such as the percentage of oxantrazole entrapped in the MCM. In association with the study design, statistical optimization procedures indicated the factors that significantly influence MCM preparation and what levels of the factors are needed to produce optimum MCM. Entrapment of anticancer agents into biodegradable microspheres is difficult because of low aqueous drug solubility and porosity of the particles. The latter effect was circumvented by a chitosan cross-linking step that resulted in approximately 3% (w/w) oxantrazole entrapment in the MCM via the optimization procedures. The combined formulation and statistical optimization strategy provide a basis to develop other microparticulate systems and led to a dosage form that can be used for future in vivo investigations.