l-Ribose has recently received attention as the starting material for nucleoside drugs. As it is not found in nature, it is being produced by enzymatic or epimerization reaction. We investigated an epimerization reaction by molybdenium oxide and examined the effects of temperature, solvent, and molybdenum oxide amount on epimerization. l-Ribose has a yield of 22% under the conditions of 100 kg/m3l-arabinose, 20% methanol, 5 kg/m3 MoO3, and 90°C. In addition, simulated moving bed (SMB) that was equipped with three NH2-HPLC columns was used to separate l-arabinose and l-ribose resulting from l-arabinose epimerization. A 3-zone SMB process was developed to eliminate the high pressure problem in the conventional 4-zone SMB. Aspen simulation was performed to determine the operating variables such as switching time, raffinate, and extract flow rates. Experimental purities of extract and raffinate were compared with the theoretical ones and they are found to be fairly well correlated.