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Heritiera littoralis Dryand were used for studying the molecular mechanisms of semi-mangroves on salt tolerance. We used two-dimensional gel electrophoresis to measure changes in the proteome in leaves of H. littoralis (the total salt content in soil of 1 g/kg (control), 10 g/kg, 19 g/kg) for 50 days. The salt treatment resulted in reductions of the seedling growth in height, Proline content, and SOD activity. There were 76 protein spots were up-regulated and 61 protein spots were down-regulated. Based on MALDI-TOFTOF analysis and NCBI database in searching the identified proteins of H. littoralis seedlings to high-salinity due to (1) Isoflavone reductase play a significant role in binding substrate; (2) The up-regulation of light-harvesting chlorophyll a-b binding protein likely helps maintain the integrity of the chloroplast protein complexes and the efficiency of photosynthesis; (3) The up-regulated of Cu-Zn SOD enzyme indicating that the antioxidative system may protect cells from oxidative damage.