Abstract. Based on the results of single factor experiments on the extraction of total flavonoids content (TFC) in roots of semi-mangrove plant Clerodendrum inerme(L.) Gaertn., operation conditions were optimized with orthogonal methodology. Four factors were applied to evaluate the extraction yield, including the ethanol concentration, extraction time, temperature and solid to liquid ratio. According to the experimental results, the influence order of different factors on the yield of TFC from the roots: ethanol concentration > solid to liquid ratio > extraction temperature > extraction time. The optimum operating parameters were determined as following, ethanol concentration of 70.0 %, extraction time of 90.0 min, temperature of 60.0 °C and solid to liquid ratio of 1:30. Under the optimized conditions, the maximal yield of TFC was enhanced to 1.279%.