Abstract: AIM：To study the pharmacokinetics of the two enantiomers of trans tramadol. METHODS: After trans tramadol hydrochloride sustained-release tablets were taken by 12 healthy volunteers in an oral multiple dosage schedule, the concentrations of (+)-trans tramadol and (-)-trans tramadol were determinated by high performance capillary electrophoresis (HPCE). The differences in serum concentrations and pharmacokinetic parameters between the two enantiomers were compared through paired t-test. RESULTS: (+)-Trans tramadol and (-)-trans tramadol in human serum were separated well. The linear range was 2.20～281.09 ng.mL^-1. The within-day and between-day RSDs were less than 10% and 15%, respectively. The relative recoveries were from 98.26% to 102.74%. The serum concentrations of (+)-trans tramadol and (-)-trans tramadol reached steady state on the fourth day in the volunteers. There were significant differences between the two enantiomers in serum concentrations at every time point and the main pharmacokinetic parameters. CONCLUSION: (+)-Trans tramadol was shown to be absorbed more completely, but eliminated more slowly in human body than (-)-trans tramadol. Pharmacokinetic studies on the two enantiomers of trans tramadol showed stereoselectivity.