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In this research, the extraction of essential oil from Calotropis Procera with the family name of Asclepiadaceae, by supercritical carbon dioxide (CO2) solvent has been investigated in detail, and the yield and chemical profile of the extracts achieved by this method were compared with those resulted by the conventional Hydro distillation method. To optimize the process parameters of CO2 supercritical extraction (SCE) of the Calotropis Procera, the Response Surface Methodology (RSM) with central composite design (CCD) was employed. The effects of temperature, pressure, and extraction time on the oil yield are considered for investigation. Results showed that the data were sufficiently fitted into the second-order polynomial model. The extraction conditions, including pressure, temperature, and extraction time, were studied between 150-200 bar, 40-50 ºC, and 50-100 min, respectively. The optimal conditions are achieved as the temperature of 47.19ºC, the pressure of 172.2 bar, and time of 86 minutes with the retrieval rate of 31.39%.