Based on the multi-threshold Otsu method, the characteristic image of granite microstructures is obtained by using the digital image processing method, and a mesoscopic model, which can reflect the actual heterogeneous structural properties, is reconstructed using Particle Flow Code. With conducting the uniaxial compressing tests based on the propoed model, the failure process and the effect of mesostructured (interface, mica, feldspar and quartz) on failure strength are analyzed. The results show that there are four types of cracks in the failure process of the granite. In the initial loading stage, cracks generate in the interface, and then in mica; when stress is close to the peak value, the cracks begin to generate in feldspar and quartz. As the strength of interface or mineral increases, the compressive strength of the granite increases, while the gradient of growth decreases. The increase of the strength of interface or the minerals can lead to a reduction in the number of cracks corresponding to the interface or the minerals, which can increase cracks in other areas. Compared to the feldspar with moderate strength and the quartz with high strength, the interface and mica are the key mesostructures that can significantly influence the granite compressive strength and failure modes. Combining Otsu digital image processing with PFC, a mesoscopic model of rocks is rebuilt, which provides an effective method for studying the mechanical properties of heterogeneous rocks.