Wellbore instability happens mostly in the shale formation. Early researches have studied thoroughly on the physicochemical and mechanical mechanism that causes instability. However, only a few works have considered the influence of field drilling operations, such as drill pipe rotation. In this paper, a true triaxial cell is used to simulate the downhole field situations, and a drill pipe rotation device is innovatively designed and implemented into the true triaxial cell. Using this facility, the influence of drill pipe rotation on shale instability has been performed. Different rotation speed, weight on bit, drilling fluid pressure, and microcracks on borehole have been considered. The enlargement of the wellbore is quantitatively plotted and compared. Results show that the drill pipe rotation contributes to a more enlargement of the wellbore, and a higher rotation speed causes a more severe collapse. The drill string weight on bit also contributes to the enlargement of the wellbore, with a larger weight on bit induces a larger diameter of the collapsed wellbore. Compared with the rotation speed and weight on bit, the influence of drilling fluid density is relatively less significant. However, the influence of microcracks caused by hitting of drilling tools is profound. For a cracked shale formation, the wellbore diameter can be enlarged for more than 40%. Then, the variation of borehole collapse with time and depth under drill pipe rotation influence is analyzed. In all of these four factors, the significant sequence is microcracks > weight on bit > rotation speed > drilling fluid pressure. In all the collapse phenomena, the collapse is more severe in the minimum horizontal stress direction. This is explained by the analysis of the stress distribution in the whole circumferential angle (360°) of the wellbore. Overall, this work fills the gap of the influence of drilling operations on wellbore instability.