Objective: Solving the problems of high feed requirement, low flow rate and poor treatment effect of industrial-scale microfluidizer （ISM） in practical application. Methods: Combining CFD-PBM simulation and emulsion preparation test, four kinds of interactive chambers were optimized, and the final shape was obtained by size optimization. Results: Four kinds of interactive chambers had larger flow rate and hole diameter than the original interactive chamber. The effect of particle size reduction was T-impact type ＞ T double impact type ＞ cross impact type ＞ two shunt type. Shear force mainly existed in the shunt zone, impact force mainly existed in the impact zone, shear force and cavitation force mainly existed in the jet zone. Turbulent motion existed in the above three zones. The geometric parameters of T-shaped impact reaction chamber were optimized to obtain the final reaction chamber model. The minimum hole diameter was 0.7 mm, and the flow rate was 878 L/h at 120 MPa. The emulsion partical size prepared by the optimized chamber was 249 nm, which was in good agreement with the simulation results. Conclusion: T-impact type interactive chamber has the advantage of particle size reduction, and the impact force is the main factor.