Shale is a typical low-permeability sedimentary rock， and wellbore stability in shale has always been a difficult and hot spot in shale gas （oil） exploration and development at home and abroad. In this paper， experimental testing， microscopic observation， theoretical analysis and numerical simulation are used to study the influence of salt solutions on the physical-chemical seepage performance of shale under shale pressure transfer experiments. Furthermore， a numerical simulation model is provided to program and reconstruct the mechanical model of particles in nanopores， and to simulate the influence of particle size， concentration， shape and fluid viscosity on shale pore plugging efficiency. The results show that： （1） Particle size and concentration can affect plugging efficiency in terms of physical plugging. When the particle size does not exceed the outlet size， with increase of the particle size from 1/5 to 1/3 and 1/2 of the outlet size， the particle blocking effect increases by 13% and 23% as particle concentration is 5wt%. （2） Change of fluid physical properties affects shale nanopore plugging. The plugging efficiency of 5 mPa·s nanoparticle solution is 16.26% higher than that of 1mPa·s nanoparticle solution. （3） In terms of chemical inhibition， the best salt solution and its concentration to prevent the transmission of shale pore pressure are 20% HCOONa. The research results can provide a good theoretical and technical basis for the selection of water-based drilling fluid systems suitable for Longmaxi shale drilling.