Intracellular　invasion　and　the　survival　of　Staphylococcus　aureus　in　phagocytic　cells　has　been　regarded　as　one　of　the　mechanisms　that　leads　to　the　treatment　failure　of　S.　aureus　infection　and　potential　antibiotic　resistance.　The　detection　of　infected　phagocytic　cells　plays　an　important　role　in　guiding　antibiotic　treatment　and　in　reducing　drug　resistance.　The　development　of　a　sensitive　and　specific　imaging　probe　to　visualize　the　intracellular　bacteria　is　quite　challenging.　In　this　work,　we　report　a　photoacoustic　agent　(MPC)　that　is　able　to　detect　intracellular　S.　aureus　infection　through　a　dynamic　process,　including　(i)　active　targeting　and　internalization　into　macrophage　cells,　(ii)　specific　molecular　tailoring　by　caspase-1　in　infected　macrophage　cells,　and　(iii)　enhancement　of　the　photoacoustic　(PA)　signal　owing　to　molecular　self-assembly.　The　PA　signal　per　area　of　the　＂stimuli-induced　assembly＂　agent　(MPC)　increases　more　than　2-fold　over　that　of　the　active　targeting　control　agent　(MPsC).　Finally,　based　on　this　approach,　the　average　PA　signal　in　the　infected　site　is　enhanced　by　approximately　2.6-fold　over　that　of　the　control　site.　We　envision　that　this　PA　contrast　agent　may　provide　a　new　approach　for　the　selective　and　sensitive　diagnosis　of　an　intracellular　bacterial　infection.