A continuous-flow integration process was developed for biodiesel production using rapeseed oil as feedstock, based on the countercurrent contact reaction between gas and liquid, separation of glycerol on-line and cyclic utilization of methanol. Orthogonal experimental design and response surface methodology were adopted to optimize technological parameters. A second-order polynomial model for the biodiesel yield was established and validated experimentally. The high determination coefficient (R-2 = 98.98%) and the low probability value (Pr < 0.0001) proved that the model matched the experimental data, and had a high predictive ability. The optimal technological parameters were: 81.5 degrees C reaction temperature. 51.7 cm fill height of catalyst KF/CaO and 105.98 kPa system pressure. Under these conditions, the average yield of triplicate experiments was 93.7%, indicating the continuous-flow process has good potential in the manufacture of biodiesel. (C) 2012 Elsevier Ltd. All rights reserved.