Starting from elemental Co (99.9%), Ni (99.9%) and Sb (99.99%) powders, Co4-xNixSb12 powder mixture with different Ni concentration were subjected to mechanical alloying by using a planetary ball mill. Phase transformation during mechanical alloying process of Co-Ni-Sb system was studied in this paper. Ni substituted skutterudite could be synthesized by solid state reaction. With assistance of hot pressing for two hours, the as mechanically alloyed low Ni concentration powders could be completely transformed into skutterudite compound. The lattice parameter of Ni substituted skutterudite compound complies well with Vegard law when x is not more than 0.2. When Ni concentration is larger than the maximum solubility, NiSb2 compound forms and single phase skutterudite compound can not be obtained.