Abstract: In order to improve propolis solubility, water-soluble propolis was prepared. The influences of the type of enzyme, reaction time, reaction temperature, pH value and the mass ratio of lipase to material on propolis solubility were studied according to orthogonal experiments of lipase hydrolysis based on the single factor experiments. Antioxidant activity of water-soluble propolis was determined by α, α-diphenyl-1-picryl-hydrazyl (DPPH) radical scavenging methods,using propolis ethanolic extracts and vitamin C as references. Results from orthogonal experiments indicated that the successive order of factors affecting the propolis enzymatic solution by lipase was mass ratio of lipase to material, reaction time, pH value and reaction temperature. The optimum lipase enzymatic conditions were obtained as follows: the ratio of added lipase 11%, the reaction time 2.25 h, pH value 5.5 and the reaction temperature 40℃. Under the optimized enzymatic hydrolysis conditions, the extraction rate of flavonoid from propolis enzymatic solution was 47.35%, and the flavonoid content was 0.4025 mg/mL. The DPPH assay showed the water-soluble propolis possessed significantly higher (IC₅₀ = 0.069 mg/mL) activity compared with vitamin C (IC₅₀=0.126 mg/mL), and slightly lower than that of propolis ethanolic extracts (IC₅₀ =0.061 mg/mL). Water-soluble propolis can be prepared by lipase hydrolysis with higher antioxidant activity.