OBJECTIVE: To screen the method for extracting total flavonoids in persimmon leaves and optimize extraction technology. METHODS: Using extract quality and flavonoids content as indexes, the effects of extracting total flavonoids in persimmon leaves by ethanol refluxing method, enzyme method (cellulase, β-glucanase and complex enzyme mixed by equal amounts of both), semi-bionic method and semi-bionic-enzyme method (the same enzymes) were compared. Using flavonoids content as index, solid-liquid radio, reflux temperature, reflux time as factors, orthogonal test was designed to optimize the extraction technology conditions of flavonoids in persimmon leaves by semi-bionic-enzyme method, and the verification test was conducted. RESULTS: The extract quantity and flavonoids content by semi-bionic-enzyme method was the highest among the 4 extraction methods, and the complex enzyme was the most suitable; the optimized extracting condition of semi-bionic-enzyme method were as follows as solid-liquid radio of 1 ∶ 14, reflux temperature of 50 ℃, reflux time of 2.0 h; extraction rates of flavonoids in 3 verification tests were 5.9%, 5.8%, 5.9% (RSD=0.98%, n=3). CONCLUSIONS: The optimized semi-bionic-enzyme method is efficient and stable in extracting flavonoids in persimmon leaves.