Mathematical modeling is necessary for the optimization and design of any separation process, such as the extraction of bio-molecules from their natural resources. The objective of this work is to obtain a quantitative description of the supercritical carbon dioxide extraction (SCDE) of andrographolide from Andrographis paniculata leaves through the development of a mathematical model based on first-order desorption rate of solute into supercritical solvent. Numerical calculations to obtain the adjustable parameter of the model, using experimental data obtained from the SCDE of andrographolide at different solvent flow rates and particle sizes, were done using MATLAB software. The results showed that this model agrees well with the experimental data. Therefore, this model is useful for the optimization and design of SCDE of andrographolide from Andrographis paniculata leaves.