Chronic　exposure　to　low-levels　of　organophosphate　(OP)　compounds,　such　as　chlorpyrifos　(CPF),　induces　oxidative　stress　and　could　be　related　to　neurological　disorders.　Hydrogen　has　been　identified　as　a　novel　antioxidant　which　could　selectively　scavenge　hydroxyl　radicals.　We　explore　whether　intake　of　hydrogen-rich　water　(HRW)　can　protect　Wistar　rats　from　CPF-induced　neurotoxicity.　Rats　were　gavaged　daily　with　6.75　mg/kg　body　weight　(1/20　LD50)　of　CPF　and　given　HRW　by　oral　intake.　Nissl　staining　and　electron　microscopy　results　indicated　that　HRW　intake　had　protective　effects　on　the　CPF-induced　damage　of　hippocampal　neurons　and　neuronal　mitochondria.　Immunostaining　results　showed　that　the　increased　glial　fibrillary　acidic　protein　(GFAP)　expression　in　astrocytes　induced　by　CPF　exposure　can　be　ameliorated　by　HRW　intake.　Moreover,　HRW　intake　also　attenuated　CPF-induced　oxidative　stress　as　evidenced　by　enhanced　level　of　MDA,　accompanied　by　an　increase　in　GSH　level　and　SOD　and　CAT　activity.　Acetylcholinesterase　(AChE)　activity　tests　showed　significant　decrease　in　brain　AChE　activity　after　CPF　exposure,　and　this　effect　can　be　ameliorated　by　HAW　intake.　An　in　vitro　study　demonstrated　that　AChE　activity　was　more　intense　in　HRW　than　in　normal　water　with　or　without　chlorpyrifos-oxon　(CPO),　the　metabolically-activated　form　of　CPF.　These　observations　suggest　that　HRW　intake　can　protect　rats　from　CPF-induced　neurotoxicity,　and　the　protective　effects　of　hydrogen　may　be　mediated　by　regulating　the　oxidant　and　antioxidant　status　of　rats.　Furthermore,　this　work　defines　a　novel　mechanism　of　biological　activity　of　hydrogen　by　directly　increasing　the　AChE　activity.　(C)　2014　The　Authors.　Published　by　Elsevier　Inc.　This　is　an　open　access　article　under　the　CC　BY-NC-ND　license.