Triclocarban　(TCC)　is　a　widely　used　antimicrobial　agent　and　known　endocrine-disrupting　chemical　found　in　various　products.　While　its　potential　toxicities　on　endocrine-related　organs　have　been　highlighted　in　previous　studies,　the　effects　of　TCC　on　non-endocrine　organs,　particularly　the　spleen,　remain　largely　unknown.　Here,　we　employed　a　novel　approach　combining　long-term　TCC　exposure　in　a　mouse　model　with　spatial　metabolomics　and　lipidomics　to　investigate　the　effects　of　TCC　on　the　spleen.　Our　results　showed　that　TCC　exposure　significantly　altered　the　splenic　organ　weight　and　coefficient　and　induced　obvious　pathological　alterations.　Omic　analysis　revealed　that　TCC　exposure　disrupted　the　splenic　homeostasis,　as　indicated　by　the　upregulation　of　glutathione　metabolism,　ceramide-to-sphingomyelin　signaling　and　biosynthesis　of　glycerophospholipids.　Notably,　the　data　of　mass　spectrometry　imaging　(MSI)　revealed　that　TCC　accumulated　in　the　red　pulp　of　the　mouse　spleen,　while　its　metabolites　concentrated　in　the　white　pulp.　Further　MSI　analyses　identified　region-specific　metabolic　disruptions,　including　upregulated　ceramide　signaling　in　the　red　pulp,　indicating　localized　inflammation,　and　upregulated　glutathione　metabolism　throughout　the　spleen,　suggesting　widespread　oxidative　damage.　Our　findings　provide　crucial　insights　into　the　spatial　distribution　and　biochemical　impact　of　TCC　on　mice　spleens,　highlighting　the　potential　risks　of　long-term　TCC　exposure　to　immune　function.　©　2024