Abstract: Effect of various factors in an ultrasound-assisted process on the polysaccharide extraction from Polygonatum filipes were studied for the technology optimization. The liquid/material ratio, temperature, as well as power and duration of ultrasonic application for the process were scrutinized. A quadratic regression rotational combinational design and the Design Expert 7.0 analytical procedures were applied to establish a regression model for projecting the maximal extraction yield under optimized conditions. Theoretically, the optimized process included the application of a liquid/material ratio of 17.81 mL/1 g at 72.97℃ with a 152.85 W ultrasonic treatment for 59.74 min to reach 16.6471% yield on polysaccharides. In a triplicated test run, an averaged polysaccharide yield of 16.59% was obtained with a liquid/material ratio of 18 mL/1 g at 73℃ with a 150 W ultrasonic treatment for 60 min. The result showed that the mathematic model was accurate in predicting the performance of the extraction process.