Macroalgae　Laminaria　japonica　(MLJ)　has　been　reported　to　exhibit　various　biological　activities　including　improving　immunity,　anti-aging,　anti-tumor,　anti-atherosclerosis　and　anti-diabetic,　but　the　protective　mechanisms　of　MLJ　consumption　against　non-alcoholic　fatty　liver　disease　(NAFLD)　associated　with　hyperlipidemia　remain　poorly　understood.　This　study　demonstrated　that　MLJ　consumption　prevented　high-fat　diet　(HFD)-induced　NAFLD　associated　with　hyperlipidemia　in　a　rat　model,　and　improved　hyperlipidemia-related　parameters,　e.g.　Serum　and　hepatic　lipid　profiles.　Moreover,　histological　analysis　showed　that　MLJ　reduced　lipid　deposition　in　adipocytes　and　hepatocytes　compared　with　the　HFD　group.　Such　beneficial　effects　may　be　associated　with　the　modulation　of　the　intestinal　microbiota,　especially　some　key　microbial　phylotypes　involved　in　lipid　metabolism　homeostasis.　The　underlying　protective　mechanisms　of　MLJ　consumption　against　HFD-induced　NAFLD　associated　with　hyperlipidemia　were　also　studied　by　ultra-high　performance　liquid　chromatography　with　quadruple-time　of　flight　mass　spectrometry　(UPLC-QTOF/MS)-based　liver　metabolomics　coupled　with　pathway　analysis.　The　metabolic　pathway　enrichment　analysis　of　the　differentially　abundant　hepatic　metabolites　indicated　that　primary　bile　acid　biosynthesis　metabolism　and　cysteine　and　methionine　metabolism　were　the　two　main　metabolic　pathways　altered　by　MLJ　consumption　when　compared　with　the　model　group.　The　analysis　of　the　transcription　levels　of　liver-related　genes　by　RT-qPCR　and　the　expressions　of　liver-related　proteins　by　immunohistochemistry　(IHC)　showed　that　MLJ　consumption　could　regulate　the　levels　of　mRNA　transcription　and　protein　expression　related　to　hepatic　lipid　metabolism.　In　short,　this　study　indicates　that　MLJ　could　be　developed　as　functional　food　supplement　for　the　prevention　or　treatment　of　NAFLD　associated　with　hyperlipidemia.　©　The　Royal　Society　of　Chemistry.