Salinity is a limiting factor affecting crop growth. We evaluated the responses of a salt-tolerant recombinant inbred rice (Oryza sativa L.) line, FL478, and the salt-sensitive IR29. Seedlings were exposed to salt stress and the growth rate was monitored to decipher the effect of long-term stress. At Day 16, IR29 produced lower shoot biomass than FL478. Significant differences for Na+ and K+ concentrations and Na+ : K+ ratios in roots and shoots were observed between genotypes. Changes in the proteomes of control and salt-stressed plants were analysed, identifying 59 and 39 salt-responsive proteins in roots and leaves, respectively. Proteomic analysis showed greater downregulation of proteins in IR29. In IR29, proteins related to pathways involved in salt tolerance (e.g. oxidative stress response, amino acid biosynthesis, polyamine biosynthesis, the actin cytoskeleton and ion compartmentalisation) changed to combat salinity. We found significant downregulation of proteins related to photosynthetic electron transport in IR29, indicating that photosynthesis was influenced, probably increasing the risk of reactive oxygen species formation. The sensitivity of IR29 might be related to its inability to exclude salt from its transpiration stream, to compartmentalise excess ions and to maintain a healthy photosynthetic apparatus during salt stress, or might be because of the leakiness of its roots, allowing excess salt to enter apoplastically. In FL478, superoxide dismutase, ferredoxin thioredoxin reductase, fibre protein and inorganic pyrophosphatase, which may participate in salt tolerance, increased in abundance. Our analyses provide novel insights into the mechanisms behind salt tolerance and sensitivity in genotypes with close genetic backgrounds.