Atherosclerosis　(AS)　is　a　common　chronic　inflammatory　disease　of　the　arteries,　which　is　closely　related　to　dyslipidemia,　inflammatory　factors,　and　oxidative　stress.　Poria　cocos　polysaccharides　(PCP)　are　one　of　the　main　active　ingredients　of　Poria,　which　has　significant　pharmacological　effects.　In　this　study,　the　potential　protective　mechanism　of　PCP　on　AS　was　discussed　in　the　ApoE-/-　mice　model　induced　by　high-fat　diet.　These　pathological　changes　were　evaluated　by　H&E　and　oil　red　O　staining.　The　levels　of　pro-inflammatory　cytokines　in　aortic　tissue　were　measured　by　enzyme-linked　immunosorbent　assay　kit.　These　protein　expressions　were　detected　by　Western　blot　and　immunohistochemistry.　The　results　showed　that　PCP　inhibited　the　serum　inflammatory　mediators　(tumor　necrosis　factor-α,　interleukin-6,　and　nitric　oxide)　and　lipids　(low-density　lipoprotein-cholesterol,　triglyceride,　and　total　cholesterol)　increase.　Moreover,　PCP　also　reduced　the　concentration　of　malondialdehyde,　increased　the　activity　of　superoxide　dismutase,　and　improved　the　pathological　changes　of　the　aorta.　Finally,　PCP　inhibited　the　activation　of　the　TLR4/NF-κB　pathway　in　the　aorta　and　blocked　the　expression　of　matrix　metalloproteinase　2　and　intercellular　adhesion　molecule　1　proteins.　In　short,　PCP　intervenes　in　AS　by　reducing　inflammatory　factors　and　blood　lipid　levels.