Using aqueous solution of acrylamide(AM) as the disperse phase, the combination of an oil soluble emulsifier (Span80) with a water soluble emulsifier (Tween80)/kerosene as the continuous phase, the phase diagram of a pseudo-ternary system was made. The inverse microemulsion was prepared according to the best aggregation point of kerosene (52.0wt%), Span80/Tween80(7.8wt%,weight ratio4:1), aqueous phase (40.2wt%) based on the pseudo-ternary phase diagram. Nanoscale polymer microspheres cross-linked with N,N-methylene bisacrylamide(MBA) were synthesized initiated by ammonium persulfate (APS) via the inverse microemulsion polymerization technique at the temperature of 70℃. Effects of the amount of cross-linker agent, initiator and stirring speed on particle size and swelling properties of crosslinked microspheres were investigated using laser diffraction particle size analysis (LPSA). The optimal synthesis conditions were determined as follows: the amount of MBA, APS were 0.60%, 0.50%, the stirring speed was 1000r/min.Swelling behavior of the microspheres obtained under the optimal conditions was discussed. It found that the maximum swelling ratio was 1690, with an absorbency of 17.90g/g in salt solution, the microspheres exhibited fine salt tolerance and high swelling ratio. The microspheres have been characterized by Fourier transform infrared spectroscopy (FT-IR), to confirm the formation of co-polymer. Transmission electron microscopy (TEM) and Scanning electron microscopy (SEM) were adopted to assess the surface morphology of particles prepared. SEM and TEM results demonstrated that polymer microspheres had distinct spherical shape, monodispersity, and uniform distribution of particle size about 200nm. Plugging performance of polymer microspheres latex was studied by the core plugging experiment, the results presented the properties of in-depth profile control step by step of plugging, breakthrough, deepening and plugging again in the cores.