Significant　impairment　of　pulmonary　function　has　been　demonstrated　through　long-term　exposure　to　neonicotinoid　insecticides,　such　as　imidacloprid　(IMI).　However,　the　underlying　mechanisms　of　lung　injury　induced　by　IMI　remain　unclear.　In　this　study,　a　mouse　model　of　IMI-induced　pulmonary　injury　was　established,　and　the　toxicity　and　lung　damage　were　assessed　through　mouse　body　weight,　organ　index,　hematological　parameters,　and　histopathological　analysis　of　lung　tissues.　Furthermore,　metabolomics　and　transcriptomics　techniques　were　employed　to　explore　the　mechanistic　aspects.　Results　from　the　toxicity　assessments　indicated　that　mouse　body　weight　was　significantly　reduced　by　IMI,　organ　index　was　disturbed,　and　hematological　parameters　were　disrupted,　resulting　in　pulmonary　injury.　The　mechanistic　experimental　results　indicate　that　the　differences　in　metabolites　and　gene　expression　in　mouse　lungs　could　be　altered　by　IMI.　Validation　of　the　results　through　combined　analysis　of　metabolomics　and　transcriptomics　revealed　that　the　mechanism　by　which　IMI　induces　lung　injury　in　mice　might　be　associated　with　the　activation　of　the　TLR4　receptor,　thereby　activating　the　PI3K/AKT/　NF-　kappa　B　signaling　pathway　to　induce　inflammation　in　mouse　lungs.　This　study　provided　valuable　insights　into　the　mechanisms　underlying　IMI-induced　pulmonary　damage,　potentially　contributing　to　the　development　of　safer　pest　control　strategies.　The　knowledge　gained　served　as　a　robust　scientific　foundation　for　the　prevention　and　treatment　of　IMI-related　pulmonary　injuries.