Abstract: Reservoir in Yanchang oilfield belongs to ultra-low permeability and low porosity reservoirs, and some fractures are well developed, the water cut rises quickly and there exists difficulty in exploitation. Therefore, by means of experimental agitation, polymer microspheres with different concentrations were prepared by experimental stirring method, the influencing factors of microspheres were analyzed from the aspects of stirring speed, reaction temperature, concentration of crosslinking agent and degree of hydrolysis. On this basis, the experimental study of plugging and flooding performance evaluation was carried out. The experimental results show that when the injected microsphere concentration is 3 000 mg/L and the injection multiple is 0.5 PV, the residual resistance coefficient and plugging rate are both high, and the plugging ability is good. The maximum reduction range of water content is 28.8%, and the recovery rate is increased by 22.7%. The field test application show that the input-output ratio is 1.00∶1.21, which has good profile modification and oil displacement and can be used for reference for similar reservoir development.