Abstract: Cefuroxime axetil micro particles were prepared by using supercritical CO₂ anti-solvent technology. With volume average particle size as the main evaluation, on the basis of single factor experiments orthogonal experimental design was used to optimize the preparation process of cefuroxime axetil particles. The experiments such as particle size distribution, scanning electro microscope analysis(SEMA), infrared spectrum(IR)and differential scanning calorimetry(DSC)were used to analyze the particles. The orthogonal experimental optimization process conditions were set as follows: crystallization pressure 10 MPa, crystallization temperature 50 ℃ and mass concentration of cefuroxime axetil 6 mg/mL, Under the optimum conditions, the volume average particle size was 6. 729 μm, IR and DSC analysis showed that the chemical structure didn′t change but the thermodynamic properties of cefuroxime axetil might transfer transform to amorphous.