[Purposes] To solve the application limitation of single-molecular-weight polypropylene glycol (PPG) in current researches on polyurethane modified asphalt, PPG-400 and PPG-2000 were compounded to prepare polyurethane modified asphalt. The optimization of preparation process and microscopic interaction mechanism were studied to provide support for its engineering application.[Methods] With 70# base asphalt as raw material, the polyurethane content was fixed at 10% and the hydroxyl number ratio of PPG-400 to PPG-2000 was set as 2:3. A three-factor and three-level orthogonal experiment was designed regarding shearing temperature, shearing rate and shearing time. Road performance was measured through conventional performance test, low-temperature bending creep stiffness test, rotational viscosity test and storage stability test. The optimal process was screened by variance analysis combined with random forest model. Fourier transform infrared spectroscopy and fluorescence scanning test were utilized to analyze the microscopic mechanism.[Findings] Shearing temperature is the critical process factor affecting the performance of modified asphalt. The optimal preparation process is determined as shearing temperature of 130 ℃, shearing rate of 4000 r/min and shearing time of 30 min. This process can collaboratively enhance the high-temperature stability, low-temperature crack resistance, rutting resistance and storage stability of asphalt. PPG-2000 is prone to cause phase separation, whereas PPG-400 can strengthen interfacial polarity interaction and improve the uniform dispersion of polyurethane.[Conclusions] The compounding of PPG with different molecular weights can adjust the interfacial effect and phase structure of PU modified asphalt, and process optimization realizes the synergistic improvement of road performance. This study clarifies the optimization rules of process and mixture ratio for PPG-based PU modified asphalt, and provides theoretical basis and technical support for its engineering application.