Abstract: OBJECTIVE To optimize the extraction process for Zhike Huatan mixture. METHODS Ultrasonic soakage-reflux extraction method was used for the extraction of medicinal plants. With the overall score of extraction rate of hesperidins and baicalin, and dry ointment yield rate as the observed index, orthogonal design was used to examine four factors including soaking time, additive water amount, reflux time and extraction times in order to optimize the extraction process. And then process certification was carried out. RESULTS The optimum extraction process was as follows:add 10 times amount of water to soak the medicine plants for 20 min using ultrasonic method, then reflux twice, 80 min for each. CONCLUSION The experimental results showed that the extraction process of Zhike Huatan mixture was stable and feasible by orthogonal test.