Cyclocarya paliurus (Batal.) Iljinsk (C. paliurus) is a very important medicinal herb in traditional Chinese medicine for the treatment of diabetes mellitus. The aim of this study was to develop an optimum extraction method of flavonoids from C. paliurus by reflux extraction. Orthogonal experimental design was used to determine the optimal extraction parameters for flavonoids from C. paliurus. The results showed that the maximum yields of flavonoids (31.16±0.96) mg/g could be obtained when the extraction time was 2 h, the extraction temperature was 80 °C, the ratio of material to solvent was 1:30 (g/mL) and 80% ethanol was used. In summary, this study provides an efficient reflux extraction for flavonoids from C. paliurus, which can be used as natural products in the pharmaceutical and functional food industries.