Temperature-resistant and salt-tolerant polymer microspheres (AMPST) were prepared by inverse emulsion polymerization using acrylamide (AM), acrylic acid(AA), 2-acrylamide-2-methyl propane sulfonic acid (AMPS) and -methyl styrene (α-MSt) as monomers. And the synthesis process of microspheres were optimized. The structure and performance of AMPST microspheres were characterized by FTIR, GPC, optical microscope, SEM, TG, rheological analyzer and core plugging experiments. The results showed that temperature and AMPS content were closely related to the initial particle size of microspheres, and temperature and initiator content determined the expansion ratio of microspheres. When the hydration temperature was 65℃ and the salinity of simulated formation water was 2.8937×103 mg/L, reaction temperature 50℃, mass of AMPS 12g, the average initial particle size of AMPST-8 microspheres was 2.01 μm, and 18.45 μm after 240 hours of hydration, with an expansion ratio of 8.18. Furthermore, AMPST-8 microspheres had smooth surface, large specific surface exhibited an aggregate state. Core plugging experiments showed that the residual resistance coefficient of AMPST-8 microspheres was 8.4 and the plugging rate was 88% after 7 days of hydration expansion in the core, higher than other microspheres provided on site. After 7 days of hydration expansion, the residual resistance coefficient and plugging rate of pilot plant product, ZS-2 microspheres were 7.8 and 87.24%, respectively.