The compound of micron powders and nanometer powders is a magnificent step in the application and development of metal matrix composite reinforced by nanometer particles. By taking nano-Al2O3 powders and Ni-based micron powders as the research object, the preparation process of metal matrix micro/nano-powders reinforced by nanometer particles with high energy ball-milling is discussed from three aspects: the additive process of nanometer powders, the additive content of nanometer powders, and the required ball-milling time in the paper. The results show that the additive process of nanometer powders which uses directly the dispersed uniformly nanometer suspensions as grinding medium can effectively decrease and avoid nanometer powders’ agglomeration of composite powders. Nanometer particles are well distributed in the composite powders. The optimum additive content of nanometer powders is consistent with the theoretical model of mixture ratio, which is determined by the ratio of the average diameter of micron powders and nanometer powders and their density of corresponding solid materials. Meanwhile, the required ball-milling time for preparation of better uniformity composite powders is no more than 0.5hr. This implies that the preparation process has a high productivity. Moreover, the preparation process is verified through other nanometer powders including nano-SiC powders and nano-CeO2 powders.