To optimize purification technology using macroporous resin for total flavonoids from lophatherum gracile with response surface method. Methods: Compare the adsorption and desorption properties of four macroporous resin on total flavonoids of lophatherum gracile. Select the appropriate resin to optimize purification process with response surface method. Results: According to the analysis of experimental data, it was better to optimize purification process with the mass concentration 0.12 g/mL of sample solution, volume fraction 75% of ethanol and eluent dosage 6BV. Conclusion: It was stable and feasible with good predictability to optimize the macroporous resin purification process for total flavonoids from lophatherum gracile with response surface method.