CO2-expanded methanol (CXM) was used to extract lipids from the microalgae Chlorella vulgaris (a total lipid content of 20.7% was determined by Soxhlet extraction with methanol at 373 K for 96 h) in a continuous mode. The CXM was found to be a superior solvent to methanol, ethanol, pressurized methanol and ethanol, and CO2-expanded ethanol for lipid extraction. The effects of operation variables including temperature, pressure and CO2 flow rate on extraction performance were examined using the response surface and contour plot methodologies. The optimal operating conditions were at a pressure of 5.5 MPa, a temperature of 358 K, a methanol flow rate of 1 mL/min and a CO2 flow rate of 3.0 mL/min, providing an extracted lipid yield of 84.8 wt% over an extraction period of 30 min. Compared with propane methanol mixture, CXM was safer and more energy efficient for lipid extraction from C. vulgaris. (C) 2015 Elsevier Ltd. All rights reserved.