Statistical experimentical designs were applied to optimize microwave-assisted extraction of puerarin from Radix Puerariae. The most important factors affecting the extraction procedure were determined using a Plackett-Burman design. Results indicated that the concentration of ethanol, solvent-material ratio, extraction time, and microwave power were the main factors affecting the extraction yield. These factors were further optimized using a central composite design and response surface methodology. The optimal extraction parameters were ethanol concentration of 52.36%, microwave irradiation time of 60s, microwave power of 184.8W and solvent-material ratio of 25:1(mL/g). The average experimental puerarin yield under the optimum conditions was found to be 11.97mg/g, which agreed with the predicted value of 11.8mg/g. The proposed method shows high degree of reproducibility.