This work focuses on the influence of changes in catalyst structure on the catalytic activity in liquid phase methanol synthesis process. Long-term methanol production experiments were performed under various reaction environments in order to investigate the relationship between the catalytic activity and the crystallite size in the methanol synthesis catalyst. The regeneration experiments were also conducted in order to reduce the crystallite size of aged catalysts by inducing metallic phase redispersion. The experimental results showed that the drop in the catalytic activity was closely linked to the growth in the crystallite size in the catalyst. The crystallite size was reduced successfully by cyclic oxidation-reduction treatments and as a result the lost activity in aged catalysts was recovered.