Nuciferine,　an　alkaloid　found　in　Nelumbo　nucifera　leaves,　alleviates　dyslipidemia　in　vivo.　However,　whether　it　improves　liver　injury　in　diabetic　conditions　and　the　underlying　mechanism　is　unclear.　The　present　study　aimed　to　investigate　the　effects　of　nuciferine　on　lipid　and　glucose　metabolism　in　a　murine　model　of　Type　2　diabetes　mellitus　(T2DM)　and　to　determine　the　underlying　mechanisms　of　these　effects.A　murine　model　of　T2DM　was　induced　by　high-fat　diet　(HFD)　feeding　combined　with　streptozocin　(STZ)　injections,　and　the　diabetic　mice　were　treated　with　nuciferine　in　their　food.　The　underlying　mechanism　of　the　anti-steatotic　effect　of　nuciferine　was　further　explored　in　HepG2　hepatocytes　cultured　with　palmitic　acid.　Major　signalling　profiles　involved　in　fatty　acid　oxidation　were　then　evaluated,　using　Western　blot,　RT-qPCR　and　si-RNA　techniques,　along　with　immunohistochemistry.Nuciferine　restored　impaired　glucose　tolerance　and　insulin　resistance　in　diabetic　mice.　Hepatic　levels　of　total　cholesterol,　triglycerides　and　LDL　were　decreased,　as　were　the　number　of　lipid　droplets,　by　nuciferine　treatment.　Furthermore,　nuciferine　up-regulated　β-oxidation　related　genes　in　livers　of　diabetic　mice.　Luciferase　reporter　cell　assay　showed　that　nuciferine　directly　reversed　palmitic　acid-induced　inhibition　of　PPARα　transcriptional　activity.　Silencing　PPARγ　coactivator-1α　(PGC1α)　expression　in　HepG2　cells　abolished　the　effects　of　nuciferine　in　accelerating　β-oxidation.Nuciferine　improved　lipid　profile　and　attenuated　hepatic　steatosis　in　HFD/STZ-induced　diabetic　mice　by　activating　the　PPARα/PGC1α　pathway.　Nuciferine　may　be　a　potentially　important　candidate　in　improving　hepatic　steatosis　and　the　management　of　T2DM.