Utilization of supercritical CO2 in safflower seed extraction was performed using a semi-batch extractor. Different extraction parameters, such as 40-60 MPa pressure, 323-347 K temperature, 20-76 min time, and 1-3 mL/min CO2 flow rate were applied. A two-stage experimental design application was performed in order to maximize the oil yield. First of all, a 3(2) factorial design was applied to estimate the effect of the main factors and their interactions. The second part of the experimental design was improved and accelerated using the steepest ascent method. Optimum extraction parameters were determined to be 50 MPa pressure, 347 K temperature and 76 min time at a constant CO2 flow rate (3 mL/min) according to the 2(2) design. Under these conditions, the oil yield obtained was 39.42%, comparable with Soxhlet extraction (40%) for 8 h. Shrinking core and empirical kinetic models were applied in order to generalize the extraction process. The predicted data was compatible with the experimental data. (C) 2014 Elsevier B.V. All rights reserved.