Abstract: Under the condition of ultrasonic assisted, the method of preparation of calcium propionate which the materials were composed of eggshell and propionic acid was studied. The effects of dilution ratio, eggshell size, reaction time, reaction temperature and ultrasonic power were researched through single- factor experiment, and the optimum conditions were investigated by the response surface methodology ( RSM) . The experimental results showed that the optimum conditions of dilution ratio was 1∶9.4, the reaction temperature was 61℃, in the ultrasonic power was 352 W, the eggshell size was 50 mesh size, and the exaction time was 2h, respectively. Under the optimum conditions, the eggshell conversion rate reached 93.91% and the purity of product reached 95.47%.