Abstract: AIM　To study the differences of the pharmacokinetics and tissue distribution of two enantiomers of nicardipine in the rabbit. METHODS　Biological samples were diluted by 1 mol·L^-1 NaOH solution and extracted with n-hexane - ethyl acetate (1:1). The concentrations of S-nicardipine and R-nicardipine in samples were determined by coupled achiral C₁₈ column (150 mm×4.6 mm, 5 μm) and chiral OJ column (250 mm×4.6 mm, 10 μm) chromatography. RESULTS　The racemic nicardipine and the enantiomers in sample were separated well by the coupled system. The linear range was 55-550 ng·mL^-1 for both enantiomers. The within-day and between-days RSD (n=5) were 5.25% and 8.97%, and the relative recoveries were 99.99% and 97.10% for R- and S- enantiomer, respectively. The mean T_max, C_max and AUC values were (2.49±0.03) h, (134±2) ng·mL^-1 and (1082±32) ng·mL^-1·h for S-nicardipine and (1.24±0.05) h, (109±2) ng·mL^-1 and (778±22) ng·mL^-1·h for R-nicardipine. The concentration of S-nicardipine were generally higher than that of R-nicardipine in main target tissues and cells. CONCLUSION There were significant differences between the two enantiomers of nicardipine in rabbit in pharmacokinetics and tissue distribution.