A novel water-soluble beta-CD-derivatized erythromycin (EM) was synthesized and used as an effective chiral selector for the resolution of chiral compounds in CZE. The purpose of substitution at the primary hydroxyl site of beta-CD with 1-oxygen-2,3-epoxypropane is to produce a compound having functions of both beta-CD and EM. beta-CD-derivatized EM exhibited excellent enantioselectivities compared with single beta-CD and EM for chiral separation in CE. We also investigated the influence of pH and concentration of BGE, concentration of chiral selector, applied potential, and organic modifier on chiral compounds' separation.