Abstract: To optimize fermentation process of puerarin Jiaosu, the puerarin was used as raw material. Based on single-factor tests, the response surface method was used to investigate the effects of processing parameters, including fermentation time, temperature, initial pH and inoculation quantity. The puerarin flavonoid contents was chosen as response value, and mathematical model was established by implementing four factors and three levels. The results showed that the model had great difference, and the established regression equation had an excellent goodness of fit. The optimum conditions were time of 72 h, temperature of 28℃, initial pH of 4.5, inoculation quantity of 2.5%. The puerarin flavonoid contents was up to 81.667 μg/mL, which was roughly follow with the predicted value (81.909 μg/mL). The influence of various factors on the contents of flavonoids was as follows:Temperature > initial pH > fermentation time > inoculation quantity.