Liquidliquid extraction (LLE) was used for the resolution of a-cyclopentylmandelic acid (alpha-CPMA) enantiomers, in which environmentally friendly and economical hydroxyethyl-beta-cyclodextrin (HE-beta-CD) was screened as the optimal selector. The mechanism on equilibrium of the separation system was proposed. Influence of important parameters on the separation performance of alpha-CPMA enantiomers were investigated (e.g., kinds of solvents for the organic phase, types and concentration of selector, pH of extraction phase, temperature). On the basis of the mechanism proposed, a quantitative model was also built to simulate the separation process. Results show that the model predicts the experimental data accurately and it is further used for optimizing the separation process. The optimized process conditions consist of 1,2-dichloroethane as organic solvent, pH = 2.5 and the extractant concentration of 0.04 mol.kg(1). Under the optimum conditions, the enantioselectivity toward alpha-CPMA enantiomers is over 1.70 and performance factor is 0.07.