High-temperature creep resistance in cations co-doped polycrystalline Al₂O₃ was examined by uniaxial compression creep test at 1250°C. The dopant oxides used in this study were 0.1 mol% of YO_1.5, ZrO₂, SrO, MgO and TiO₂. The creep rate in Al₂O₃ was significantly changed by cations co-doping. For instance, Zr/Y co-doping suppressed the creep rate in Al₂O₃ by a factor of about 400. A high-resolution transmission electron microscopy (HREM) and nano-probe energy dispersive X-ray spectroscopy (EDS) analysis revealed that Y and Zr cations segregate along grain boundaries. The grain boundary diffusion in Al₂O₃ was supposed to be retarded by the segregation of Y and Zr cations. A first-principle molecular orbital calculation was made for cations co-doped Al₂O₃ and cation singly doped Al₂O₃ model cluster. The creep rate was correlated with the value of net charge in oxygen anion. The net charge of oxygen anion was one of the most important factors to determine the creep resistance in Al₂O₃.