Epilepsy　with　recurrent　seizures　is　characterized　by　neuronal　damage　and　glial　proliferation　induced　by　brain　inflammation.　Recurrent　seizures　can　lead　to　changes　in　the　microRNA　(miRNA)　spectrum,　significantly　influencing　the　inflammatory　response　of　microglia.　MiR-155–5p,　as　a　pro-inflammatory　miRNA,　is　increased　in　the　epileptic　brain.　However,　its　specific　role　in　acute　seizures　remains　unknown.　The　study　aimed　to　develop　a　new　strategy　for　treating　epilepsy　by　investigating　how　silencing　of　miR-155–5p　initiated　its　anticonvulsive　mechanism.　The　level　of　miR-155–5p　was　up-regulated　in　the　hippocampus　of　epileptic　immature　rats　induced　by　kainic　acid　(KA).　The　use　of　antago-miR-155–5p　exerted　significant　beneficial　effects　on　the　seizure　scores,　brain　discharges　and　cognition　in　immature　rats　following　KA-induced　epilepsy.　Antago-miR-155–5p　also　inhibited　neuron　damage　and　microglial　activation.　Moreover,　the　silencing　of　miR-155–5p　significantly　inhibited　the　Dual-specificity　phosphatase　14　(Dusp14)/　mitogen-activated　protein　kinase　(MAPK)　axis　in　vivo.　MiR-155–5p　interacted　with　dusp14　to　regulate　MAPK　signaling　way　expression,　verified　by　a　dual-luciferase　reporter　assay.　The　results　suggested　that　the　silencing　of　miR-155–5p　might　reduce　hippocampal　damage　in　epileptic　immature　rats　induced　by　KA　via　Dusp14/MAPK　signaling　way.　This　implied　that　miR-155–5p　could　serve　as　a　therapeutic　tool　to　prevent　the　development　of　epilepsy.　©　2024　The　Authors