Abstract: Differential pressure activated sealant is a new technology suitable for rapid and safe repair of micro leakage in tubular strings in oil and gas wells. There are few reports on the application and theoretical research of this system. Based on a combination of laboratory test, structural characterization, theoretical analysis and numerical simulation, this paper systematically carries out basic research for application in terms of preparation, micro-morphology detection, sealing property evaluation, mechanism analysis of differential pressure activation, as well as dynamics simulation of adaptive sealing. The research results show that the prepared differential pressure activated sealant is a polydisperse system; the dispersed phase is hydrated colloidal particles with micron-level layered physical conformation, which is a key component to ensure the sealing property of differential pressure activated sealant. Within the pressure differential range of 5-15 MPa, in 150 s, the sealant can penetrate the threaded dropout and leaky pores to form a tough solid barrier, which can effectively plug different types of micro-defects. Based on the relationship between the molecular morphology and stability of the hydrated colloidal particles, this paper proposes a hypothesis on the structure effect of liquid-solid transformation of differential pressure activated sealed fluid, and establishes an adaptive sealing mechanics-chemical coupling model of the differential pressure at the leaking point. Further, it analyzes the stress state of composite droplet under the differential pressure of environmental liquid, uses the LES-VOF method to simulate the dynamic behaviors of deformation and breaking of the composite droplet in the jet flow field of environmental liquid, explores the dynamic evolution process of the dehydration of hydrated colloidal particles. The jet deformation on the surface hydration shell is significantly larger than that of the colloidal nucleus, and thus wave breaking occurs, resulting in the elimination of surface hydration shell and the activation of colloidal nucleus, which will facilitate filling blockage of micro-defects. The simulation results are basically consistent with the theoretical analysis, which provides a theoretical support for further researches on the differential pressure activated sealant.