In the recent few years, the measurement, correlation, and calculation of solid solubility, especially drugs, in supercritical fluids have been increased. Evaluation of solubility of a solid solute drug in supercritical fluids is a major factor in the production of nanosized particles. In this research, the solubility of repaglinide (RPL; antidiabetic drug) was measured for the first time. Experiments was fulfilled at various temperatures (308-338 K) and pressures (120-270 bar). It was found that the solubility of RPL is within the range of 2.899 X 10-6 to 9.529 X 10-5. Peng Robinson and UNIQUAC as well as six semi -empirical models, including Sodeifian et al., Bartle et al., Chrastil, Mendez-Santiago Teja, Garlapati Madras, and Kumar Johnston, was applied to model the solubility behavior. Moreover, self-consistency tests were carried out to discover the RPL solubility in SC-CO2. Finally, the approximate values of total (A1-1,01j, vaporization (AH p), and solvation (A11,01) enthalpies were computed.