The microstructural evolution of Al-Zn-Mg-Zr alloy with trace amount of Sc during homogenization treatment was studied by means of metallographic analysis, scanning electron microscopy (SEM), energy dispersive X-ray (EDX) and differential scanning calorimetry (DSC). The results show that serious dendritic segregation exists in studied alloy ingot. There are many eutectic phases with low melting-point at grain boundary and the distribution of main elements along interdendritic region varies periodically. Elements Zn, Mg and Cu distribute unevenly from grain boundary to the inside of alloy. With increasing the homogenization temperature or prolonging the holding time, the residual phases are dissolved into matrix α(Al) gradually during homogenization treatment, all elements become more homogenized. The overburnt temperature of studied alloy is 476.7 °C. When homogenization temperature increases to 480 °C, some spherical phases and redissolved triangular constituents at grain boundaries can be easily observed. Combined with microstructural evolution and differential scanning calorimeter, the optimum homogenization parameter is at 470 °C for 24 h.