In order to reveal the mechanisms of cell osmo-adaptation to salt stress, a newly identified moderately halophilic Bacillus sp. I121 was used to study the salt-stress responding proteins. Differential proteomic analysis of the purified plasma membrane fractions were performed by two dimensional Blue-Native/SDS-PAGE. Eight proteins corresponding to NaCl were identified by MALDI-TOF/TOF. Up-regulated proteins under salt stress include an ABC transporter permease, glycerol-3-phosphate permease, pyrimidine nucleotide transporter, formate dehydrogenase, and down-regulated proteins include succinate dehydrogenase iron-sulfur subunit, flavoprotein subunit, cytochrome b-556 subunit, and a hypothetical membrane protein similar to charperone DnaJ. Some of these changes were further verified by enzyme activity assay. Most of these proteins are highly hydrophobic trans-membrane protein, and responsible for material transport across membrane and energy metabolism. These results indicated that in halophilic Bacillus sp. I121, higher salt stress activated material transport across plasma membrane, and compatible solutes, such as proline and ectoine, could be synthesized through suppressed TCA cycle. The research further demonstrated that besides the protein complexes in mitochondria and chloroplast, BN/SDS-PAGE is also a powerful tool for the protein complexes in plasma membrane.