Abstract: This paper aimed to explore the changes in sesame phenolics and antioxidant activity and the correlation between the two after simulating in vitro digestion of sesame treated with ultra-high static pressure and different pressures, and observe the microstructure changes of sesame with rheometer and scanning electron microscope. The results showed that the contents of sesame lignans, total phenols and total flavonoids after different pressure treatments were significantly higher than those of untreated ones. The total lignans, total phenols and antioxidant activity composite index (ACI) of 200 MPa treated sesame samples were (30.20±1.20) mg/100 g, (473.04±13.73) µmol Rutin/100 g and (88.02±3.80) µmol Rutin/100 g, which were significantly higher than the untreated value. Regardless of the content of phenolic substances and the strength of antioxidant capacity, 200 MPa was an ideal treatment condition. The rheological characteristic curve showed that the viscosity was maximum when the pressure was 600 MPa, and the sesame structure became more stable. It was observed by scanning electron microscope that with the pressure change, the surface of the sample became loose and porous, and at the same time, it promoted the action of digestive enzymes, which was beneficial to improve the digestibility.