OBJECTIVE: To optimize microwave-assisted aqueous two-phase system of total flavonoids from Glycyrrhiza uralensis. METHODS: The ammonium sulfate and ethanol were used as aqueous two-phase extraction system, the method of microwave was applied to extract total flavonoids from G. uralensis. The effects of 5 factors on extraction rate of total flavonoids were investigated by single factor test and orthogonal test, such as the mass concentration of ammonium sulfate, ethanol volume fraction, solid-liquid ratio, microwave power and extraction time. Validation test was conducted. RESULTS: The optimal extraction condition was as follows as the mass concentration of ammonium sulfate of 0.40 g/ml, ethanol volume fraction of 70%, solid-liquid ratio of 1 ∶ 25, extraction time of 3 min and microwave power of 300 W; in validation test, the extraction rate of total flavonoids from G. uralensis was 2.038% (RSD=0.69%, n=3), and the extraction rate of two-phase system was 94.46% (RSD=1.30%, n=3). CONCLUSIONS: The technology is simple in operation and stable in results, and also has gentle reaction conditions and high extraction rate, which is suitable for industrial production.