A novel method for the determination of enantiomers of three N-heterocyclic drugs was developed by revered phase high performance liquid chromatography using cellulose-tris-（4-methylbenzoate） as chiral stationary phase（CSP）. Enantioseparation of oxazepam,pioglitazone and rosiglitazone on the CSP were performed by using mixture of methanol and water as mobile phase. Effects of methanol-water ratio,pH value and temperature on chiral separation of three drugs were investigated,respectively.The results showed that their enantiomers were separated on the CSP with methanol-0.01% acetic acid solution（50∶50） at 25 ℃ under pH 6.0 for oxazepam, methanol-0.01% ammonia solution（60∶40） at 30 ℃ under pH 8.0 for pioglitazone,and methanol-0.01% ammonia solution（65∶35） at 40 ℃ under pH 8.0 for rosiglitazone,respectively. The mechanism of racemic resolution for three drugs was discussed.The proposed method was successfully applied in the determination of three drugs enantiomers in commercial tablets,with recoveries and relative standard deviations（RSDs） of 94.6% -106.2% and 0.07%-1.0%,respectively.It was proved to be simple,reliable and accurate.