The　rapid　identification　of　bacterial　antibiotic　susceptibility　is　pivotal　to　the　rational　administration　of　antibacterial　drugs.　In　this　study,　cefotaxime　(CTX)-derived　resistance　in　Salmonella　typhimurium　(abbr.　CTX(R)-S.　typhimurium)　during　3　months　of　exposure　was　rapidly　recorded　using　a　portable　Raman　spectrometer.　The　molecular　changes　that　occurred　in　the　drug-resistant　strains　were　sensitively　monitored　in　whole　cells　by　label-free　surface-enhanced　Raman　scattering　(SERS).　Various　degrees　of　resistant　strains　could　be　accurately　discriminated　by　applying　multivariate　statistical　analyses　to　bacterial　SERS　profiles.　Minimum　inhibitory　concentration　(MIC)　values　showed　a　positive　linear　correlation　with　the　relative　Raman　intensities　of　I-990/I-1348,　and　the　R-2　reached　0.9962.　The　SERS　results　were　consistent　with　the　data　obtained　by　MIC　assays,　mutant　prevention　concentration　(MPC)　determinations,　and　Kirby-Bauer　antibiotic　susceptibility　tests　(K-B　tests).　This　preliminary　proof-of-concept　study　indicates　the　high　potential　of　the　SERS　method　to　supplement　the　time-consuming　conventional　method　and　help　alleviate　the　challenges　of　antibiotic　resistance　in　clinical　therapy.