Ethanol production using Zymomonas mobilis strains with medium optimized by response surface methodology (RSM) was studied. A significant improvement in the ethanol yield (0.50g/g ethanol) was demonstrated, resulting in very low residual sugar and fewer by-products. The five-factor and five-response full factorial design have shown that glucose and yeast extract are the hey media components that influence ethanol production, follow-ed by the inoculum concentration and ammonium sulfate, with phosphate showing Little or no effect. The composition tall in g/l of the optimized medium was glucose 120.4, ammonium sulfate 0.96, potassium dihydrogen phosphate 0.02, yeast extract 6.5, and magnesium sulfate 0.5. The optimum inoculum concentration was log(10) 8.4 cells.