Monascus vinegar (MV) exerts beneficial effects on cardiovasular diseases. The present work explored the lipid-lowering mechanism of MV and the correlation among gut microbiota, lipid metabolism and inflammation. The results illustrated that the administration of MV ameliorated hyperlipidemia by regulating Peroxisome proliferator-activated α (PPARα)-, Nuclear factor-E2-related factor 2 (Nrf2)- and Nuclear factor κB (NF-κB)-mediated signals and modulating the gut microbiota composition in hyperlipidemia rats. Moreover, Lactobacillus, Roseburia and Lachnostridium showed positive correlation with antioxidative parameters and negative correlation with lipid metabolism and inflammation parameters. Whereas Clostridium, Desulfovibrio and Streptococcus exhibited the opposite effect. Importantly, the differences in lipid-lowering effect between high-dose of MV (HD) group and low acetic acid and lovastatin (LLA) group were evaluated, which indicated that the other components in MV could improve the lipid-lowering effect of acetic acid and lovastatin. Our findings provided a novel insight into the lipid-lowering effect of MV.