Abstract: AIM To investigate the transportation of the enantiomers of trans tramadol (trans T) and its active metabolite, O-demethyltramadol (M₁) across blood-brain barrier. METHODS Rats were sacrificed by femoral artery bleeding 1 h after ip administration of trans T hydrochloride, 16.7 mg·kg^-1 or 50. 0 mg·kg^-1. Blood, cerebrospinal fluid and cerebral cortex were taken out. The enantiomers of trans T and M₁ were analyzed by high performance capillary electrophoresis (HPCE). RESULTS Among the three tissues, the concentration of each enantiomer of trans T and M₁ was the highest in the cerebral cortex, and the lowest in the cerebrospinal fluid. In the serum, the concentration of (+)-trans T was higher than that of (-)-trans T, and the concentrations of the enantiomers of M₁ were similar. In the cerebrospinal fluid and cerebral cortex, the concentration of (+)-trans T was higher than that of (-)-trans T, and the concentrations of (+)-M₁ was lower than that of (-)-M₁. CONCLUSION The transportation across blood-brain barrier of the enantiomers of trans T and M₁ was stereoselective. In the brain tissues, the concentrations of (+)-trans T and (-)-M₁ were higher than those of their enantiomers.