During the shut-in treatment after hydraulic fracturing, the interaction between the water-based fracturing fluid and the reservoir rock can cause the swell of clay minerals. This can alter the stress condition of the rock, thus activating and expanding the natural fractures in the shale reservoir. However, it is currently controversial whether the effect of water-rock interaction on shale permeability is positive or negative under different closure stresses.To investigate this effect on natural fractures and rock permeabilities under closure stress, imbibition experiments are conducted, and the nuclear magnetic resonance (NMR) T2 spectrum is continually scanned to identify the fracture formation.Results show that the water-rock interaction can activate and expand the natural fractures, resulting in increases of 20.0%–61.6% in rock permeability during the spontaneous imbibition without closure stress; as the percentage of clay minerals increases in shale samples, the degree of rock permeability enhancement also increases. Meanwhile, during the forced imbibition without closure stress (i.e., centrifuge), increases of 1.14–46,912 times in rock permeability are observed, indicating that higher imbibition pressure (or pore pressure) results in a greater degree of rock permeability enhancement. However, when the closure stress exists, the increase of shale permeability during the forced imbibition is only 8.3%–11.5%, even though the activation and expansion of natural fractures are observed; this indicates that the closure stress can hinder the activation and expansion of natural fractures, thus hinders the enhancement of shale permeability by the water-rock interaction.Experimental results of this study indicate the stress condition can significantly affect the impact of water-rock interaction on natural fractures and shale permeability; therefore, operators should consider this effect when designing the shut-in time after hydraulic fracturing to maximize the oil recovery rate.