BACKGROUND Chlorogenic acid is an important bioactive substance with wide pharmacological effects mostly related to scavenging free radicals and as an anti-virus. This article reports on the continuous separation of chlorogenic acid from Eucommia ulmoides crude extract using multistage centrifugal fractional extraction. RESULTS An efficient extraction system was constructed. A quantitative mathematical model was established to simulate and optimize the fractional extraction process, and the optimum process conditions were obtained. Residual rate was successfully introduced as the purity reference to optimize the separation of chlorogenic acid. Chlorogenic acid was continuously obtained from Eucommia ulmoides extract by fractional extraction in a cascade of ten stages with high purity of 97.2% and yield of 81.4%. CONCLUSION Fractional extraction is an efficient and likely unique technology to continuously and selectively separate target substance from complex natural extract. It has the advantages of large output and low cost, and is more suitable for industrial-scale production. (c) 2020 Society of Chemical Industry