Abstract: Slaking, a common engineering characteristic, is the main weathering mode from clay-bearing rocks to soils. Due to the influences of wetting-drying cycles of natural climate, mudstone can slake and disintegrate into the grains with different sizes, which cause numerous problems of erosion and slope instability. Thus, studying the influence factors for the strength attenuation of mudstone in the process of slaking and disintegration is of great engineering significance. On the basis of the red mudstone with low strength and weak expansion in the lower part of the waterway slope in the in-situ test project of the water diversion of the Yangtze River to Huaihe River in China, a method for disintegration tests regarding natural constrained condition is developed to study the variation characteristics of fracture development, particle composition, disintegration ratio, shear resistance and strength parameters. The results show that there is a critical number of wetting-drying cycle effects. Before the seventh wetting-drying cycle, the parameters of mudstone samples change significantly, including increase of fissures, percentage of fine particles, reduction of disintegration ratio, reduction of shear resistance and reduction of strength parameters. After the seventh wetting-drying cycle, the changes of these parameters are not obvious. The characteristics of the disintegration behaviors are independent of the critical grain size D_cr of the complete disintegration, and the decreasing trends of the disintegration index I_Di and disintegration ratio D_R are similar. The highly positive correlation between the strength parameters and the disintegration ratio D_R indicates that wetting-drying cycles are the factor that induces rock slaking, and the particle composition and state changes of samples play a role in the strength attenuation, and the disintegration resistance rate is a quantitative index of particle composition and state.