Objective:To observe the effect of 2,3,4’,5-tetrahydroxystilbene-2-O-β-D-glucoside (TSG) on hyperlipidemic fatty liver in rats,and explore the potential mechanisms by PPAR α signaling pathway. Methods:SD rats were randomly divided into control group,model group,TSG 80 mg/kg group,MK886 plus TSG 80 mg/kg group. The rat model was established by orally feeding high-fat emulsion for 4 weeks. Then TSG was administered to these rats for 6 weeks. TC,TG and FFA levels in serum and hepatic tissues,hepatic weight coefficient,the levels of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)in serum were measured;and the hepatic histopathological changes were observed. Meanwhile,the expressions of PPAR α,LC3Ⅰ,LC3Ⅱ,Beclin 1 and p62 proteins in hepatic tissues were measured by Western blot. Results:Compared with the model group,TSG could significantly decrease TC,TG and FFA levels in serum,TG and FFA contents in hepatic tissues,hepatic weight coefficient,and also the serum levels of ALT and AST(P<0.05 or P<0.01). Meanwhile,the histological evaluation of liver specimens revealed that lipid accumulation in TSG-treated group was obviously ameliorated. Western blot results showed that TSG could markedly up-regulated the expressions of hepatic PPAR α,LC3Ⅱ,Beclin 1 proteins,and down-regulated the expression of p62(P<0.05 or P<0.01). However,the effect of TSG was weakened or cancelled when pretreatment with PPAR α antagonist MK886. Conclusion:TSG was effective in treating hyperlipidemic fatty liver in rats,and its mechanism might be related to the up-regulation of LC3Ⅱ and Beclin 1 protein expressions,down-regulation of p62 protein expression to activate autophagy by activation of PPAR α,and eventually to improve lipid metabolism.