The effects of process parameters on the extraction of Ginkgo biloba L. leaves with supercritical carbon dioxide were investigated. The investigated parameters include particle size (mean particle diameter 0.19, 0.467 and 1.009 mm), solvent flow rate (1.5810-3, 3.2210-3 and 4.1610-3 kg CO2/min) and pressure (100-300 bar), which were obtained by the response surface methodology (RSM) under the following condition ranges: temperature 40-50-60ºC, pressure 100-140-180 bar and extraction time of 2-3-4 h at the flow rate of 3.2210-3 kg/min. Based on the experimental results of kinetics of Ginkgo biloba leaves extraction with supercritical carbon dioxide, modeling of the extraction system of Ginkgo biloba-supercritical CO2 was done. Two mathematical models (Reverchon-Sesti Osseo and Sovová) were applied to correlate the experimental data. RSM was applied to optimize the process parameters of supercritical carbon dioxide extraction of Ginkgo biloba L. leaves. A second-order polynomial response surface equation was developed indicating the effect of variables on Ginkgo biloba extraction yield. The statistical analysis of the experiment indicated that pressure (X1), extraction time (X3), the quadratic of temperature (X22), and the interaction between pressure and extraction time (X1X3), show significant effect on the extraction yield. The results showed that the data were adequately fitted into the second-order polynomial model. It was predicted that the optimum extraction process parameters within the experimental ranges would be the extraction temperature of 52.7ºC, the pressure of 184.4 bar, and the extraction time of 3.86 h. Under these conditions, the predicted extraction yield is 2.39% (g/100 g drug)