An experimental and simulated study of the fractionation of Ligusticum chuanxiong via adsorption in supercritical carbon dioxide (SC-CO2), using silica gel as the adsorbent, was conducted. Adsorption equilibrium and adsorption dynamic data were obtained from experiments conducted at 8.8 MPa and 323.15 K. The adsorption isotherms can be represented by the Extended Langmuir 1 isotherm equation. Effect of the flow rate of the strippant was studied, and the regeneration became more complete and occurred more quickly as the flow rate of the strippant increased. Highly concentrated fraction of lactone was obtained for the desorption step and the recovery of it reached 85%. A mathematical model simulated the behavior of the process well, and the amount of adsorbed components on the adsorbents was predicted graphically.