This study was designed to investigate the mechanism of polyphenol-enriched extract of Rosa rugosa Thunb (RPE) in the control of dyslipidemia in diabetic rats. RPE was tested at three dosages (37.5 mg/kg, 75 mg/kg and 150 mg/kg) in the rat dyslipidemia model established with high fat diet feeding in combination with STZ injection (30 mg/kg). The RPE effect was evaluated after 4 weeks of treatment. In the RPE-treated rats, hepatic total cholesterol (TC) and triglyceride (TG) were significantly reduced, lipoprotein lipase (LPL) and liver lipase (HL) were significantly increased. The levels of alanine transaminase (ALT) and aspartate transaminase (AST) were decreased in the serum. Those effects of RPE were observed primarily at the mediate and high dosages. Expression of FGF21 was increased in the liver tissue and hepatic cell line 1c1c7 by RPE. The signals of p-AMPK, p-ACC, ACC, p-SIRT, and PGC-1 alpha were significantly induced in the liver by RPE. The results suggest that RPE may improve hepatic steatosis and liver function by induction of AMPK signaling activity in the control of dyslipidemia.