To study the relationship of macroscopic physical characteristics and microscopic cracks of interbedded sandstone. 2D particle flow code (PFC2D) is accustomed to exploring the strength, failure mode, and micro-crack evolution with distinct inclinations (beta) under uniaxial compression. The results show that the stress-strain curve of interbedded sandstone can be divided into the elastic, yielding, and crack propagation stages. The strength of the specimens is a U-shaped curve with increasing beta. When tensile failure (0 degrees, 15 degrees, 30 degrees, and 90 degrees) occurs, the interbedded effect coefficient (S-(beta)) is a minimum. The micro-cracks mainly accumulated at a uniform rate in the early stage with a uniform crack distribution, and pre-peak multi-peak phenomenon occurs. When composite failure (45 degrees) occurs, the S-(45 degrees) is maximum. In the later stage, the variation of micro-cracks is nonlinear growth periodically. Meanwhile, the inclination gradually increases, the post-peak multi-peak phenomenon occurs. Shear failure (60 degrees and 75 degrees) occurs, with a few micro-cracks, primarily in the interlayer in the early stage. The micro-cracks propagate fast and the inclination is directional, when macroscopic damage occurs in specimens, and post-peak multi-peak phenomenon occur. The results can be used as a guide for similar structures' instability warning and stability control.