In order to study the influence of stress paths on the macroscopic and microscopic mechanics response of sandstone, the hollow cylinder sample was constructed based on the particle discrete element method. The six experiments of different stress paths were conducted, and the macroscopic stress-strain response and microscopic normal and tangential contact force distribution were investigated. The results show that when the internal confining pressure is the same, with the increase of the external pressure, the volume strain of the sample also increases, that is, the expansion of the sample becomes more obvious. When the outside pressure of the sample is the same, with the increase of internal confining pressure, the volume strain of the sample increases first and then decreases. When the coefficient of intermediate principal stress is not 0, the absolute value of the sum of radial strain and circumferential strain of the sample increases with the coefficient of intermediate principal stress. When the internal confining pressures are same, the normal contact force of the sample increases with the outside pressure. When the outside pressures are same, the normal contact force of the sample decreases with the internal confining pressure.