Abstract: There are large sections of sandstone-shale interbedding in East China Sea region, where mudstone is extremely prone to hydration expansion. With the development of micro fractures, it is very easy to encounter complex situations such as tripping resistance and torque suppression, and even wellbore instability. Meanwhile, the use of oil-based drilling fluids was limited due to the environmental restriction. In order to solve the issue of borehole instability in East China Sea, high concentration salt was used to reduce the activity of the system in laboratory based on the theory of oil-based drilling fluids activity balance and semi-permeable membrance. At the same time, the inhibitive ability of the system is enhanced and micro & nano-sealing technology is used to effectively delay the transfer of pressure and filtrate. Finally, a set of reverse osmosis drilling fluid system with similar properties to oil-based drilling fluid was developed through indoor performance comparison and evaluation. The field application results of this system showed that its performance was stable during drilling, with regular cuttings and stable wellbore, and basically achieved direct tripping, reduced the frequency of wellbore instability in mudstone formations in East China Sea.