Effect of different organic solvents for isolation of glabridin from Glycyrrhiza glabra L. has been evaluated and the optimum solvent was obtained. On the basis of single-factor test,the response surface methodology with 3 factors and 3 levels was adopted. The ultrasound-assisted extraction process parameters of glabridin from Glycyrrhiza glabra L. were optimized by the quadratic general spinning design on the ratio of solvent to solid,extraction time and ultrasonic power. The yield of glabridin was used as the responsive values. The results indicate that the optimum conditions for glabridin are as follows:solvent is ethyl acetate,extraction 2 times,ultrasonic power is 500 W,extracting time is 30 min,the ratio of solvent to solid is 23∶1 (mL/g),and extracting temperature is 44 ℃,the maximum yield of glabridin is 0.269%. The validation test shows that the prediction values of the model are well agreed with the experimental values.