Objective To observe the effects of Akkermansia muciniphila (AKK) on lipid metabolism and inflammatory factors in ApoE knockout (ApoE-/-) mice fed with high-fat diet. Methods Healthy SPF male C57BL/6J and ApoE-/- mice (4 weeks old) were selected and fed with high-fat diet. Six weeks later, 20 ApoE-/- mice with an average weight higher than 10% of that of C57BL/6J mice were selected and numbered randomly, and those with odd number were divided into the model group (n=10) and those with even number into the AKK intervention group (n=10). And another 10 C57BL/6J mice served as control group. The mice in the control group and the model group were intragastrically administrated with glycerol preparation without AKK, and those out of the AKK intervention group were given glycerol preparation containing 1×10⁹CFU AKK, 0.1 ml each time, once per day. After intragastric administration for 4 weeks, fasting body weight was measured. Serum and epididymal adipose tissues were collected from each group. Serum levels of triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), interleukin-1 (IL-1), IL-6, IL-8, IL-10, C-reactive protein (CRP), tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein-1 (MCP-1) were detected. The weight of epididymal adipose tissue was weighed, and the morphology was observed after HE staining to calculate the average size of epididymal adipose tissue cells. SPSS statistics 26.0 was used for data analysis. One-way analysis of variance was used for comparison among multiple groups. Results After 4 weeks of intragastric administration of AKK, the fasting body weight, epididymal fat weight and body fat percentage were decreased in the AKK intervention group than the model group, though the differences not significant (P>0.05). The AKK intervention group had significantly lower TG (0.85±0.17 vs 1.65±0.15 and 1.08±0.09 mmol/L) and LDL-C levels (3.20±0.85 vs 6.47±0.87 and 4.89±0.56 mmol/L), and obviously higher HDL-C (919.89±116.19 vs 433.59±183.85 and 721.11±222.70 mmol/L) when compared with the model group and the control group (all P<0.05). The TC level was notably lower in the intervention group than the model group (3.00±0.64 vs 5.12±0.71 mmol/L, P<0.05). For the inflammatory factors, the levels of IL-1 (74.10±25.28 vs 191.42±31.36 and 123.91±25.29 pg/ml), IL-6 (63.10±9.53 vs 100.76±11.42 and 77.76±8.20 pg/ml), IL-8 (64.34±10.36 vs 104.59±8.46 and 82.64±11.79 pg/ml), CRP (88.85±24.33 vs 172.53±25.41 and 122.72±22.08 ng/ml), TNF-α (372.30±47.05 vs 674.53±62.18 and 509.97±54.50 pg/ml) and MCP-1 (11.90±1.58 vs 25.18±2.03 and 18.59±2.11 pg/ml) in the AKK group were remarkably lower than those in the model group and control group (all P<0.05). The IL-8 level was in a trend of increasing, but no statistical differences were seen among the 3 groups (P>0.05). HE staining showed that the average area of epididymal adipocytes was significantly smaller in the AKK intervention group than the model group (330.45±55.84 vs 879.58±36.74 μm², P<0.05), and regular cell morphology and increased number of adipocytes in a single field of vision were also observed. Conclusion AKK improves dyslipidemia and reduces serum inflammatory factors in obese ApoE-/- mice fed with high-fat diet.