Abstract: Because of aiming at high formation water salinity and extra-low permeability in Block Wuliwan Changqing oilfield, traditional stimulation measures in EOR were difficult to implement. So the polymeric nanospheres flooding technology was discussion in this paper. Using the particle size analyzer and transmission electron microscopy, based on the single sand packs model and the real core visual micro-model and parallel sand packs macro-model, the adaptability of polymeric nanospheres flooding in extra-low permeability reservoir was studied from the aspects of the swelling, injection of polymeric nanospheres, water-permeability reduction as well as laboratory simulated flooding of polymeric nanospheres. The experimental results proved that the polymeric nanospheres had good injection and could swell in formation water. The expanded nanospheres could selectively reduce the water phase permeability of the high-permeability sand packs, and made fluid diverting to effectively displace residual oil and enhance the oil recovery greatly. The polymeric nanospheres flooding could be an effective stimulation measure of production in the extra-low permeability reservoir of Block Wuliwan Changqing oilfield. The research provides experimental basis for further applications of polymeric nanospheres in oil field.