Objective: To investigate the effects of tea blend composed of Enshi selenium-rich tea, gynostemma pentaphyllum and apenma on blood lipid and lipid metabolism in mice with hyperlipidemia and prevention of hyperlipidemia in mice on the high-fat diet. Methods: Mice were randomized into 7 groups, among which 6 groups were fed with high-fat diet to establish a hyperlipidemia mouse model, and the other group was fed with normal diet as the normal control. After the hyperlipidemia model was established, mice were fed with normal diet while receiving different regimens. The normal diet group, the high-fat control group and the positive control group were given physiological saline solution, physiological saline solution and atorvastatin daily by gavage, respectively. The initial intervention group was given medium dose tea blend solution by gavage, and the other three groups were given low, medium and high dose of tea solution daily by gavage, respectively. After 4 weeks of treatment, mice were sacrificed, blood samples were taken for monitoring of lipid metabolism, -liver and tissue tissues were removed for examination of morphology and gene expression. Results: The tea blend not only significantly reduced the level of blood lipid in hyperlipidemia mice, but also effectively protected the liver and kidney function (P < 0.05). Observation under the light microscope reveled that, high-fat diet led to the accumulation of fat in hepatocytes and disorder of hepatic cordage, while the tea blend alleviated the hepatocyte steatosis. In addition, the tea blend promoted the expression of HL and HSL genes, and increased the levels of LAXR and PPARA, which regulated lipid metabolism at the genetic level (P < 0.05). Conclusion: This study confirmed that drinking tea blend composed of Enshi selenium-enriched tea, Gynostemma pentaphyllum and Apocynum venetum could lower blood lipids in mice with hyperlipidemia. In addition, various doses of tea blend could be used for hyperlipidemia with good liver and kidney function, and medium or high dose of tea blend was relatively safe for hyperlipidemia with poor liver and kidney function.