In this work, S-bupivacaine with the pharmacological activity of epidural anaesthesia was separated from R-bupivacaine by SMB (simulated moving bed). Nonlinear isotherm was suggested from the single column experiment and the mass transfer coefficient was obtained from an empirical equation. The parameters of a in competitive Langmuir adsorption equation empirically determined by PIM (pulsed input method) for R and S-bupibacaine were 6.20, 8.79 respectively, while those of b were 0.364, 0.922 ml/mg, respectively. These equilibrium and kinetic parameters were used by a commercially available simulator to find the optimum operating condition for resolving the two racemic mixtures. It was experimentally confirmed that based on these experimental conditions, the separation of bupivacaine enantiomers was successfully performed with the purity of more than 98% by SMB composed of eight column (2-2-2-2, 1×10 cm) packed with Kromasil^® CHI-TBB.