Insulin has a key role in the treatment of diabetes mellitus, which is growing into epidemic proportions worldwide. For the treatment of type I diabetes and many patients with type II diabetes, injection of one or more doses of intermediate - or long- acting insulin is necessary to satisfy the patient’s basal requirement of insulin. Diosgenin is one of the most important precursors in the synthesis of steroidal drugs, and it has been reported to possess many pharmacological activities, such as antidiabetic activity, anticancer, cardiovascular action and antimalarial activities. It also plays an important role in the control of plasma cholesterol level. Tribulus terrestris L. is one of the most important resources for diosgenin production. The occurrence of saponins, flavonoids,onand temperature had significant effects on the recoveries of essential oil and diosgenin. It was predicted that the optimum extraction conditions within the experimental ranges would be the extraction pressure of 23.3 MPa and temperature of 47.7 with flow rate of 0.74 ml/min and extraction time of 130.9 min. Under such conditions, the recoveries of essential oil and diosgenin were predicted to be 91.63% and 86.12%, respectively. Moreover, in the present study, a mathematical modeling for extraction of diosgenin from T. terrestris fruit using supercritical carbon dioxide was performed. The model was developed utilizing diffusion-controlled regime in the pore and film mass transfer resistances with axial dispersion of the mobile phase at dynamic conditions. The mass transfer parameters, i.e., effective pore diffusivity, film mass transfer coefficient and axial dispersion, along with the solubility parameter were chosen as the model parameters. The first three mass transfer parameters were predicted using nondimensional equations from the literature. Henry law was used to describe the equilibrium state of solid and pore fluid phases. Genetic algorithm was applied to determine the optimal value of Henry coefficient such that to minimize the absolute average deviations ( AAD ) between the experimental and predicted extraction recoveries. The values of absolute average deviations ( AAD ) were in the range of 2–8.44%, which is the indication of a very good compatibility and validation for the developed model. Key Words Supercritical extraction, Diosgenin, Tribulus terrestris , Response surface methodology, Mathematical modeling