Modelling and optimization of the extraction of St. John's Wort using supercritical fluid is the subject of this study. Applying conservation of mass, two partial differential equations were written for solute concentration in both solvent and solid phase. The equilibrium constant of St. John's Wort extract between solid and solvent phase was determined using genetic algorithm optimization technique. The differential equations were solved using numerical techniques simultaneously and were compared with experimental data. The results showed a good agreement between model results and experimental data. Simulation and optimization according to genetic algorithm have shown that 313 K and 20 MPa were the optimum temperature and pressure for supercritical carbon dioxide extraction of St. John's Wort. (C) 2011 Elsevier B.V. All rights reserved.