Two CFD models A and B were developed based on APV high-pressure homogenizer and it was determined that the mathematical model and analysis method of B were more consistent with the actual homogenization process. The internal flow field of the high-pressure micro-jet homogenizer was simulated using Fluent software. The homogenization pressure, ratio of oil to water, and temperature were investigated. The optimal parameter combination obtained from numerical simulation of orthogonal experiment was 20 degrees C, 70 MPa, and 1:12. APV high-pressure homogenizer orthogonal experiment was conducted and the optimal experimental parameter combination obtained was 50 degrees C, 70 MPa, and 1:15. The two groups of optimal parameters were used in the homogeneous experiments. TEM images were used for comparative analysis of the particle size, and the particle size obtained by numerical simulation was slightly larger. A comparison of experimental and numerical simulation results indicate that the single factor experiment and the orthogonal experiment were not entirely chime. The reason for the discrepancy is because the emulsifier was added in the homogeneous experiment such that there were more flow field variation factors in the homogenization process and the numerical process did not define all relevant conditions. However, the highly similar development trend verifies the effectiveness of the B model, which can provide an important reference in the development and use of homogenizers.