"Witches' broom" Disease caused by the "Candidatus phytoplasma aurantifolia” is one of the important citrus disease that causes significant economic losses in Iran, western Asia and North Africa. In this study the effect of disease stress on leaf proteome was investigated. Leaf samples were collected from plants and were analyzed using 2-DE coupled with MS. The power of 2DE for proteins separation makes it possible to study various qualitative and quantitative changes in protein expression under normal and stress condition. out of 801 leaf proteins from eight biological replicates of healthy and infected plants that were analyzed by melani6 software, 63 proteins showed a significant response to the disease. MS results indicated that 19 proteins were involved in oxidative stress defense photosynthesis, metabolism and the stress response. Identifying these proteins can reveal newer response pathways and the genes that control them. The results of this study can be used in mexican lime breeding programs.