Wellbore instability in oil and gas drilling is resulted from both mechanical and chemical factors. Hydration is produced in shale formation owing to the influence of the chemical property of drilling fluid. A new experimental method to measure diffusion coefficient of shale hydration is given, and the calculation method of experimental results is introduced. The diffusion coefficient of shale hydration is measured with the downhole temperature and pressure condition, then the penetration migrate law of drilling fluid filtrate around the wellbore is calculated. Furthermore, the changing rules of shale mechanical properties affected by hydration and water absorption are studied through experiments. The relationships between shale mechanical parameters and the water content are established. The wellbore stability model chemical-mechanical coupling is obtained based on the experimental results. Under the action of drilling fluid, hydration makes the shale formation softened and produced the swelling strain after drilling. This will lead to the collapse pressure increases after drilling. The study results provide a reference for studying hydration collapse period of shale.