Abstract: Objective To evaluate the therapeutic effect of propolis against Triton-WR1339-induced hyperlipidemia in mice andexplore the underlying mechanism. Methods C57BL/6 mice were randomly divided into 7 groups (n=10), including the controlgroup, hyperlipidemia model group, fenofibrate (30 mg/kg) treatment group, and 4 treatment groups treated with low- (30 mg/kg)or high-dose (60 mg/kg) propolis HB01 or HB02. In all but the control group, acute hyperlipidemia models were established byintramuscular injection of Triton WR-1339, and corresponding treatments were administered via gastric lavage for 7 days.After the treatments, blood samples were collected for testing the levels of total cholesterol (TC), triglycerides (TG), highdensitylipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), malondialdehyde (MDA), superoxidedismutase (SOD), alanine aminotransferase (GPT), and aspartate aminotransferase (GOT); Western blotting was used to detectthe expressions of the proteins involved in lipid metabolism in the liver tissues including ABCA1, ABCG8, LDLR, and SR-B1.Results Compared with the normal control group, the mice with Triton-WR1339-induced hyperlipidemia showed significantlyincreased levels of TC, TG, LDL, MDA, GPT, and GOT and lowered HDL-C levels and SOD activity (P<0.05). Treatments withfenofibrate and the 2 propolis at either low or high dose significantly reversed Triton-WR1339-induced changes in blood lipids(P<0.05), and the effects of propolis were more potent. Triton-WR1339 injection also significantly decreased the expressionslevels of ABCA1, ABCG8, LDLR, and SR-B1 in the liver (P<0.05), and these changes were obviously reversed by treatmentswith fenofibrate and propolis (P<0.05), especially by the latter. Conclusion The lipid-lowering effects of propolis are mediatedby improving lipid metabolism and regulating the expressions of lipid transport proteins in the liver tissue.