Abstract: The effects of blueberry enzyme on dysregulated lipid metabolism and intestinal microbiota in hyperlipidemic mice were investigated, using blueberry juice as a control, they were divided into normal group, model group, simvastatin group, high-dose blueberry Jiaosu group, medium-dose blueberry Jiaosu group, low-dose blueberry Jiaosu group, and blueberry juice group. After 4 weeks of drug intervention, the mice's weight, serum lipid levels, organ changes and the liver function of each group mice were measured, and the pathological sections of liver, kidney and colon were also monitored. Then, the effect of blueberry Jiaosu on the composition, relative abundance and diversity of intestinal flora in the feces of hyperlipidemic mice was analyzed by 16S rRNA high-throughput sequencing. The results indicated that blueberry Jiaosu could inhibit the weight gain in mice (P<0.05). Blueberry Jiaosu decreased the serum levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) content in the serum of hyperlipidemic mice (P<0.01), increased the level of high-density lipoprotein cholesterol (HDL-C) in serum (P<0.01), and reduced the organ weight of heart, liver and kidney (P<0.01), and alanine transaminase (ALT) and aspartate aminotransferase (AST) activities to protect liver tissues and organs (P<0.01). The blueberry juice group had no significant effect on the body weight of mice, and there was no significant difference in TC, TG, LDL-C, HDL-C content between the high-fat diet group and the blueberry juice group. Liver, kidney, and colon tissue lesions were significantly improved by blueberry Jiaosu. Tissue damage was normalized, and hyperlipidemia symptoms were alleviated. Carbohydrate-metabolism, amino acid metabolism, and energy metabolism capacities of the intestinal microflora were affected. The abundance and diversity of intestinal microbes were regulated, while structural composition of intestinal microbiota in hyperlipidemia mice was changed.