Abstract: Isoquercitrin is a class of alcohol-soluble natural products from mulberry leaves that widely presents in the nature belongs to flavonoids. As a natural colorant, antioxidant and functional food ingredient, it widely used in the food and pharmaceutical industries because of the biological activity of lowering blood pressure, reducing blood fat, antioxidant and antiviral. But extracting isoquercetrin from mulberry leaves is difficult because of tissue structures in the plants which composed of lignin, cellulose and hemicellulose. However, hydrothermal reaction with high temperature and high pressure is beneficial to the transformation and decomposition of plant tissues. To reduce the mass transfer resistance of the active ingredients dissolved from plant tissue, method of hydrothermal-assisted alcohol was therefore proposed to increase the extraction rate of isoquercitrin from mulberry leaves simultaneously. Depending on a single-factor experiment, the appropriate ranges of extraction parameters were decided, such as hydrothermal time, hydrothermal temperature, ethanol content, and the solid-liquid ratio. A detailed discussion was made on various affecting factors like hydrothermal time, hydrothermal temperature, ethanol content and the solid-liquid ratio with the Box-Behnken design. After this, the diffused model was built to study the process of isoquercitrin leaching in solid-liquid mass transfer. And surface functional group of the raw material before and after reaction was characterized by FTIR. The results of single-factor experiment showed that the ranges of the hydrothermal time were 40-80 min, the hydrothermal temperature was 120-160℃, the content of ethanol was 50% - 70% and the solid-liquid ratio was 1:5-1:7, respectively. While the optimum parameters were based on results of optimization through response surfaces. That's mean that ethanol and mulberry leaves weight ratio was 7:1, ethanol content was 57%, after 80 min of hydrothermal-assisted alcoholic extraction under 154℃, the concentration of isoquercetin could finally reach 3.649 1 mg/g with 5.0 g mulberry leaves. It was 51 times as much as alcohol extracting which the concentration only reached 0.071 0 mg/g. The values calculated by the model agreed well with the parallel experiments results, and the maximum error between test value and the predicted value was less than 1.3%. Furthermore, the order of all the factors that affected the extraction rate of isoquercitrin was as follows: hydrothermal time > hydrothermal temperature > ethanol content > solid-liquid ratio, and all the quadratic response surface regression models had a good accuracy and predictive ability (R2=0.958 2, R2Adj=0.916 3, P<0.000 1). Using Webber-Morris dynamics model to explore the mass transfer process of isoquercitrin leaching, three processes of boundary diffusion, internal diffusion and infiltrated stage in the diffused process of isoquercitrin in hydrothermal system were obtained, respectively, indicating that the diffusion of isoquercitrin was complicated, and internal diffusion was the main control step process, but not the only speed control step. The boundary layer had a certain influence on the diffusion, and the effect of the liquid boundary layer increased with increasing concentrations of isoquercitrin. The order of C (thickness of the boundary layer) value was CI