Abstract: To investigate and optimize the ultrasound- assisted extraction procedure for the water- soluble Polysaccharide from the Flos Populi,important variables and their levels were obtained using Plackett- Burman design and Box- Behnken design.A mathematical model was developed to show the effects of each variable and their combinatorial interactions on extraction yield of Polysaccharide. A high coefficient of determination( R2=98.77%) indicated good agreement between the experimental and predicted values of Polysaccharide yield. The optimum levels of these significant parameters were determined using response surface methodology( RSM),which revealed these as follows: ultrasonic output power 195 W,extraction temperature 66 ℃,extraction time43 min. Under these conditions,63.18 ± 1.57 mg / g of polysaccharide was extracted,which had a difference of2% ~3% with the predicted value.