In this paper, cationic polyacrylamide microspheres (CPAM) were synthesized using acrylamide (AM) and methacryloyloxyethyl trimethyl ammonium chloride (TMAEMC) as monomers, ammonium sulfate as dispersant, poly(acryloyloxyethyl trimethyl ammonium chloride) (PAETAC) as dispersion stabilizer, and ammonium persulfate as initiator. The synthetic method was dispersion polymerization. The effects of monomer ratio (AM/TMAEMC), dispersant concentration, and dispersion stabilizer dosage on dispersion polymerization were systematically studied to determine the optimal preparation conditions. The structure and viscosity of the synthesized polymer were characterized by FTIR and capillary viscometry, respectively, and the particle sizes and distribution of the polymer microspheres were characterized by microscopy and dynamic light scattering, respectively. Finally, flow tests were conducted to measure the permeability reduction performance of the microspheres at various concentrations in sand packs with different permeability. Results show that CPAM emulsion of a solids content of 1wt% has excellent performance in low-to-medium permeability formations (< 1,000 mD), and the efficiency may reach above 90%.