To investigate the lipid-lowering effects and underlying mechanisms of Rosa rugosa flowers polysaccharide (RRP) on hyperlipidemic rats, 60 male SD rats were randomly divided into six groups (n=10): normal control, high-fat diet model, simvastatin, and low-dose, medium-dose, and high-dose RRP groups. A hyperlipidemia model was established by feeding a high-fat diet. After four weeks of continuous administration, body weight, liver index, and abdominal fat were measured. Lipid contents in serum and liver tissues were determined by colorimetric methods. Hepatic oxidative stress and inflammatory levels were assessed by colorimetry and ELISA. Histopathological changes of the liver were observed by HE staining and oil red O staining. RT-qPCR was used to detect the expression levels of lipid-related genes in the liver. Compared to the high-fat diet model group, body weight, liver index, and abdominal fat weight were significantly decreased in all RRP-treated groups in a dose-dependent manner (P<0.05 or P<0.01). Serum total cholesterol, triglycerides, and low-density lipoprotein cholesterol levels were markedly reduced, while high-density lipoprotein cholesterol was significantly elevated (P<0.05 or P<0.01). RRP promoted cholesterol clearance and transformation by upregulating the mRNA expression of low-density lipoprotein receptor (LDLR) and cholesterol 7α-hydroxylase (CYP7A1) and downregulating the mRNA expression of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR). Meanwhile, it inhibited the mRNA expression of lipogenic genes including sterol regulatory element-binding protein 1c (SREBF1), fatty acid synthase (FASN), and acetyl-CoA carboxylase (ACACB), while activating fatty acid oxidation-related genes peroxisome proliferator-activated receptor alpha (PPARA), carnitine palmitoyltransferase 1A (CPT1A), and acyl-CoA oxidase 1 (ACOX1) (P<0.05 or P<0.01). Moreover, RRP significantly increased hepatic antioxidant enzyme activities, reduced oxidative stress levels, and inhibited the nuclear factor kappa B (NF-κB) signaling pathway (P<0.05 or P<0.01), thereby alleviating inflammation. These results indicate that RRP exerts significant lipid-lowering and potential hepatoprotective effects, providing a scientific basis for its development as a natural therapeutic agent for hyperlipidemia.