Acute　cadmium　toxicity　induces　multi-system　organ　failure.　Mass　spectrometry　(MS)-based　omics　analyses　and　atmospheric　pressure　matrix-assisted　laser　desorption/ionization　mass　spectrometry　imaging　(AP-MALDI　MSI)　are　powerful　tools　for　characterizing　the　biomarkers.　Many　studies　on　cadmium　toxicity　by　metabolomics　have　been　investigated,　whereas　the　applications　of　lipidomics　and　MSI　studies　are　still　inadequate.　In　this　study,　the　systematic　metabolomics　study　on　female　ICR　mice　tissues　including　liver,　kidney,　heart,　stomach,　brain　as　well　as　spleen　under　cadmium　exposure　was　firstly　conducted　and　lipidomic　characterizations　on　female　ICR　mice　liver,　kidney　and　heart　were　further　constructed　step　by　step.　To　deeply　understand　its　toxicological　mechanisms,　several　representative　lipids　on　the　mouse　liver　were　visualized　by　AP-MALDI　MSI.　The　results　demonstrated　that　exposure　to　cadmium　caused　significant　metabolic　alterations　in　the　liver,　kidney　and　heart　among　all　the　tissues.　Additionally,　the　toxicological　mechanisms　of　cadmium　in　the　mouse　models　are　closely　associated　with　the　inflammation　response,　energy　expenditure,　oxidative　stress,　DNA　and　mitochondria　damage,　and　lipid　homeostasis.　These　insights　could　enhance　knowledge　in　acute　cadmium　toxicity　of　public　health　and　guide　risk　assessment　in　the　future.　(c)　2021　Published　by　Elsevier　B.V.