The response surface methodology was used to optimize the ultrasonic extraction of Ganoderma lucidum polysaccharides. Design expert analysis indicated that the optimal processing conditions were: ultrasounic power 320 W, temperature 70 ℃ and extraction time 34 min, respectively. The extraction yield and the ORAC value of polysaccharide were 2.78% and 1956 μmol Trolox/g, respectively, which had no significant differences with the predicted values, indicating that the response surface methodology was a reasonable method to optimize the extraction conditions of Ganoderma lucidum polysaccharides. The molecular weights distribution of the polysaccharides under the optimal conditions were 18150 Da (20.07%) and 6484 Da (79.93%), much less than those of the polysaccharides prepared by traditional water extraction.