Monascus?vinegar?(MV) is a typical?fermented food?with various health-promoting effects. This study aimed to evaluate the role of MV in alleviating high-fat-diet-induced inflammation in rats with?hyperlipidemia?and elucidate the possible regulatory mechanisms. In the study,?serum lipid?profiles, liver pathology and liver inflammatory cytokines were analyzed in hyperlipidemia rats with MV (0.5 mL/kg?mb, 2 mL/kg?mb). Results showed that the administration of MV alleviated?dyslipidemia?by decreasing the serum and liver levels of?triglyceride?and?total cholesterol. Increase in?hepatic lipase?and?carnitine palmitoyl transferase 1?(CPT-1) levels and decrease in hepatocyte?steatosis,?nephritis, and intestinal tissue injury in the HD group showed that high-dose MV can significantly suppress hepatic?lipid accumulation?and steatosis. In addition, compared with the model (MOD) group, the HD group showed significantly down-regulated the level of serum or hepatic?alanine aminotransferase?(ALT), aspartate aminotransferase (AST), CPT-1, interleukin (IL)-2, IL-6, IL-12, and?tumor necrosis factor α?(TNF-α). Moreover, the HD group showed repressed hepatic nuclear factor κB (NF-κB) pathway and inactivated phosphatidylinositol 3-kinase (PI3K)/?protein kinase B?(Akt)/mammalian target of rapamycin (mTOR) pathway mitigated liver inflammation. Similar results were obtained from cell experiments. Collectively, these findings revealed that MV might attenuate high-fat-diet-induced inflammation by inhibiting the NF-κB and PI3K/Akt/mTOR pathways.