[Objective] To study the effects of Nostoc sphaeroids Kütz polysaccharide (NSKP) on blood lipid and gut microflora in high fat diet mice.[Methods] The healthy 8-week-old male mice were assigned into 5 groups, with 10 mice in each group. The normal group included the C57/6CNC mice administrated with normal saline by gavaged with standard diet, and the control group consisted of ApoE^-/- mice administrated with normal saline by gavaged with standard diet. The model group consisted of the ApoE^-/- mice administrated with normal saline by gavage and fed with high-fat and high-cholesterol diet. The ApoE^-/- mice in the low-dose and high-dose NSKP groups were fed with high-fat and high-cholesterol diet and received 0.4 g/kg and 0.8 g/kg BW NSKP, respectively. The experiment lasted for 22 weeks, and then the serum, liver, colon tissue, and cecal contents samples were collected from the mice. Serum lipid level was measured by the biochemical analyzer. The tissue structure and fat deposition were observed via HE staining and oil red O staining, respectively. The diversity and composition of gut microflora in cecal contents were analyzed by 16S rRNA gene high-throughput sequencing and bioinformatics tools.[Results] NSKP reduced the serum lipid level and fat deposition in liver tissue, and improved the diversity and relative abundance of gut microflora in high-fat diet mice.[Conclusion] NSKP can improve lipid metabolism and regulate gut microecological balance in high-fat diet mice.