Natural variability of stress tolerance in halophytic plants is of significance both ecologically and in view of identifying molecular traits for salt tolerance in plants. Using ecophysiological and proteomic analyses, we address these phenomena in two Tunisian accessions of the oilseed halophyte, Cakile maritima Scop., thriving on arid and semi-arid Mediterranean bioclimatic stages (Djerba and Raoued, respectively), with a special emphasis on the leaves. Changes in biomass, photosynthetic gas exchange and pigment concentrations in C. maritima plants treated with three salinity levels (0, 100 and 300mM NaCl) were monitored for 1month. Comparative two-dimensional gel electrophoresis (2-DE) revealed 94 and 56 proteins of differential abundance in Raoued and Djerba accessions, respectively. These salinity-responsive proteins were mainly related to photosynthesis and oxidative phosphorylation (OXPHOS). Although Djerba accession showed a lower biomass productivity, it showed a slightly higher CO2 assimilation rate than Raoued accession when salt-treated. Photosynthesis impairment in both accessions under salinity was also suggested by the lower abundance of proteins involved in Calvin cycle and electron transfer. A significant increase of protein spots involved in the OXPHOS system was found in Djerba accession, suggesting an increase in mitochondrial respiration for increased ATP production under saline conditions, whereas a lesser pronounced trend was observed for Raoued accession. The latter showed in addition higher abundance of proteins involved in photorespiration. Salt-challenged plants of Djerba also likely developed mechanisms for scavenging ROS in leaves as shown by the increase in superoxide dismutase and thioredoxin, while an opposite trend was found in Raoued.