Objective: A conductor like screening model for real solvents (COSMO) was used to predict the extraction of emodin from Polygonum multiflorum in solvents, to screen the best extraction solvent, and to explain the extraction mechanism. Methods: The COSMO model was used to predict the extraction of emodin from Polymonium multifum by natural deep eutectic solvents (NADESs) prepared with 1, 3-propylene glycol-lactic acid (1∶3) and traditional deep eutectic solvents(DESs), and the accuracy of the model prediction was verified by experiments. The extraction mechanism was further explained. Results: The COSMO model prediction, emodin and 1, 3-propanediol-lactic acid (1∶3) NADES interactions for 762.897 2 kJ/mol, significantly higher than that of emodin and interaction energy between methanol and water, the greater the interaction energy, the higher extraction efficiency, The extraction efficiency of emodin was predicted to be 1, 3-propanediol-lactic acid (1∶3)＞ methanol ＞ water. Further test validation that the extraction yield of emodin by NADES was 1.126 6 mg/g, and the extraction efficiency was 16.07 times that of water and 1.19 times that of methanol. The overall trend was consistent with the predicted results of COSMO model. Conclusion: COSMO model not only can accurately predict the dissolution rule of emodin in different solvents, also can be explained from the Angle of the micro extraction mechanism, can provide all kinds of natural products efficiently provide certain reference for the selection of extraction solvent.