Objective To optimize the preparation method of oridonin liposomes. Methods The liposomes were prepared by the ethanol injection method with cholesterin and soybean lecithin as carriers. The envelope efficiency of oridonin liposomes was taken as the observation index to optimize the preparation by orthogonal design. Results Oridonin:phospholipid was 1∶20, cholesterol: phosphatidylcholine was 5∶1, sonication time was 20 min, and temperature was 50 ℃. Conclusions The method is suitable for producing liposome using oridonin, and its form is integrated.