Knee　osteoarthritis　(KOA)　is　a　highly　prevalent,　chronic　joint　disorder,　and　it　is　a　typical　disease　which　can　develop　chronic　pain.　Our　previous　study　has　proved　that　endocannabinoid　(2-AG)-CB1R-GABA-5-HT　pathway　is　involved　in　electroacupuncture　(EA)　mediated　inhibition　of　chronic　pain.　However,　it　is　still　unclear　which　among　the　5-HT　receptor　subtype　is　involved　in　EA　evoked　5-HT　mediated　inhibition　of　chronic　pain　in　the　dorsal　spinal　cord.　5-HT2A　is　a　G　protein-coupled　receptor　and　it　is　involved　in　5-HT　descending　pain　modulation　system.　We　found　that　EA　treatment　at　frequency　of　2　Hz　+1　mA　significantly　increased　the　expression　of　5-HT2A　receptor　in　the　dorsal　spinal　cord　and　intrathecal　injection　of　5-HT2A　receptor　antagonist　or　agonist　reversed　or　mimicked　the　analgesic　effect　of　EA　in　each　case　respectively.　Intrathecal　injection　of　a　selective　GABA(A)　receptor　antagonist　Bicuculline　also　reversed　the　EA　effect　on　pain　hypersensitivity.　Additionally,　EA　treatment　reversed　the　reduced　expression　of　GABA(A)　receptor　and　KCC2　in　the　dorsal　spinal　cord　of　KOA　mice.　Furthermore,　we　demonstrated　that　intrathecal　5-HT2A　receptor　antagonist/agonist　reversed　or　mimicked　the　effect　of　EA　up-regulate　of　KCC2　expression,　respectively.　Similarly,　intrathecal　injection　of　PLC　and　PKC　inhibitors　prevented　both　anti-allodynic　effect　and　up-regulation　of　KCC2　expression　by　EA　treatment.　Our　data　suggest　that　EA　treatment　up-regulated　KCC2　expression　through　activating　5-HT2A-Gq-PLC-PKC　pathway　and　enhanced　the　inhibitory　function　of　GABA(A)　receptor,　thereby　inhibiting　chronic　pain　in　a　mouse　model　of　KOA.