Chronic alcohol consumption induces hepatic steatosis, the early stage of alcoholic liver disease (ALD). The aim of present study is to investigate the protective effect of Panax notoginseng saponins (PNS) against chronic ethanolinduced hepatic steatosis in vivo. Mice were pairfed a modified LieberDeCarli liquid diet containing alcohol or isocaloric maltose dextrin as control diet with or without PNS (200 mg/kg, BW) for 8 weeks. Animals supplemented with PNS were protected against hepatic lipid accumulation induced by chronic ethanol exposure. Accordingly, PNS could significantly decrease the elevation of plasma triglyceride, plasma enzyme activities, i.e. alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and hepatic TNF-α and IL-6 levels which were induced by chronic alcohol exposure. In addition, PNS markedly reduced the lipolysis of white adipose tissue (WAT) that stimulated by alcohol feeding through the inhibiting protein expression of phosphorylation of hormonesensitive lipase (pHSL), rather than total HSL. Furthermore, alcohol exposure also enhanced fatty acid uptake capacity in liver by elevated hepatic CD36 expression, which could attenuated by PNS treatment. These results demonstrate that PNS supplementation protects against chronic ethanolinduced hepatic steatosis, which is associated with ameliorating dysfunctional lipid metabolism of WAT and the reduced inflammatory cytokines. Our findings suggested that PNS might be potential to be developed as an effective agent for the treatment of chronic alcoholic steatosis. © 2014 Journal of Chinese Pharmaceutical Sciences, School of Pharmaceutical Sciences, Peking University.