Pore pressure transmission is one of the important mechanisms for the instability of mud shale wellbore, and nano-micron scale graphene oxide research provides a new way for pore shale plugging. The pore structure of Longmaxi formation mud shale in Sichuan was characterized by scanning electron microscopy (SEM) and nitrogen adsorption; Graphene oxide (GO) with thickness of 1.2 nm and average slice size range from 197 nm to 969.9 nm was prepared by modified Hummers method, and its plugging performance was evaluated by pressure transmission experiments; Based on SEM and X-ray energy dispersive spectroscopy(EDS) tests of shale after plugging, the main mechanism of GO plugging shale core was discussed. The results show that GO with size of 969.9nm and mass fraction of 0.1% has the most obvious effect of resisting pressure transmission; The transmission time of 1MPa differential pressure is 1000s, while the transmission time of distilled water is 30s; GO which is a semi-transparent flocculent film stacked on the surface of the core filled and sealed core nano-micron pores.