Non-alcoholic　fatty　liver　disease　(NAFLD)　is　the　most　common　chronic　liver　disorder.　Glaucocalyxin　A　(GLA)　is　a　diterpenoid　compound　that　possesses　various　activities.　In　the　study,　we　explored　the　effect　of　GLA　on　high　fat　diet　(HFD)-induced　fatty　liver　and　fibrosis.　We　showed　that　GLA　significantly　inhibited　hepatic　steatosis　and　decreased　the　hepatic　level　of　triglyceride　and　total　cholesterol　and　serum　level　of　alanine　aminotransferase　and　aspartate　aminotransferase　in　HFD-fed　mice.　GLA　significantly　inhibited　the　increase　of　hydroxyproline,　mRNA　expression　of　alpha-smooth　muscle　actin　(alpha-SMA)　and　transforming　growth　factor-beta　1　(TGF　beta　1)　induced　by　HFD　in　vivo　and　PA　in　vitro.　Moreover,　GLA　decreased　the　level　of　proinflammatory　cytokines　in　livers　of　HFD-fed　mice　and　PA-treated　hepatocytes.　Decrease　of　sirtuin　1　(SIRT1)　expression　induced　by　HFD　and　PA　was　inhibited　by　GLA.　Furthermore,　knockdown　of　SIRT1　suppressed　the　inhibitory　effect　of　GLA　on　lipid　accumulation,　inflammation　and　fibrosis-biomarkers.　The　data　in　our　study　showed　that　GLA　protected　against　fatty　liver,　inflammation　and　fibrosis.　Upregulation　of　SIRT1　was　responsible　for　GLA-induced　inhibition　of　lipid　accumulation,　inflammation　and　fibrogenesis.　Overall,　our　study　demonstrated　that　GLA　may　be　a　promising　choice　for　the　therapy　of　fatty　liver　and　fibrosis.