Lycopene belongs to the carotenoid family with high degree of unsaturation and all-trans form. Lycopene is easy to isomerize and auto oxide by heat, light, oxygen and different food matrices. With an increasing understanding of the health benefit of lycopene, to enhance stability and bioavailability of lycopene, ultrasonic emulsification was used to prepare lycopene microcapsules in this article. The results optimized by response surface methodology (RSM) for microcapsules consisted of four major steps: (1) 0.54 g glycerin monostearate was fully dissolved in 5 mL ethyl acetate and then added 0.02 g lycopene to form an organic phase, 100.7 mL distilled water which dissolved 0.61 g synperonic pe(R)/F68 as the aqueous phase; (2) the organic phase was pulled into the aqueous phase under stirring at 60 °C water bath for 5 min; (3) the mixture was then ultrasonic homogenized at 380 W for 20 min to form a homogenous emulsion; (4) the resulting emulsion was rotary evaporated at 50 °C water bath for 10 min under a pressure of 20 MPa. Encapsulation efficiency (EE) of lycopene microcapsules under the optimized conditions approached to 64.4%.