Statistical experimental design and bioreactor strategies were applied to enhance CO2 fixation ability of microalga Scenedesmus obliquus CNW-N. Four operating parameters strongly influencing microalgal CO2 fixation efficiency (namely, CO2 concentration, CO2 flow rate, magnesium concentration, and light intensity) were optimized with response surface methodology. The optimal range of parameters achieving the best overall performance of specific growth rate and CO2 fixation rate was determined with overlay counter plot techniques. Optimal ranges of CO2 concentration, CO2 flow rate, magnesium concentration and light intensity were 2.0-2.5%, 0.3-0.5 vvm, 1.7-2.7 mM and 180-250 mu mol m(-2) s(-1), respectively, achieving a specific growth rate of >1.22 d(-1) and CO2 fixation rate of >800 mg L-1 d(-1). Semi-batch operations further enhanced the biomass productivity, photosynthesis efficiency, and CO2 fixation rate to 1030 mg L-1 d(-1), 10.5%, and 1782 mg L-1 d(-1), respectively. This performance is better than the results reported by most related studies. (C) 2011 Elsevier Ltd. All rights reserved.