To study the effect and mechanism of propolis flavonoids and its effective component on the regulation of lipid metabolism. MethodsThe effect of propolis flavonoids on serum lipids (TG, TC and HDL-C) and the key enzyme in lipid metabolism (HL and 7CYP7A1)were tested in hyperlipidemia rat model and primary cell line (hepatocyte and adipocyte) respectively; and the effect of the active component from propolis flavonoids on insulin resistance was observed in vitro as well. Results The levels of TG and TC in propolis flavonoids group were significantly decreased compared with the group of hyperlipidemia model (P<0.05). The levels of HL and 7CYP7A1were significantly increased compared with the group of hyperlipidemia model (P<0.05) in vitro. The effective component of propolis flavonoids, including 7-methylchrysin, quercetin-3-O-neohesperidin and caffeic acid, increased the glucose consumption in L6myotubes (P<0.05). Moreover, 7-methylchrysin in the dose of 0.4μg/ml and quercetin-3-O-neohesperidin in the dose of 10μg/ml could significantly reduce free fatty acids absorption in L6myotubes. Conclusion The mechanism of propolis flavonoids on the regulation of lipid disorders might be depend on the regulation of the key enzyme in lipid metabolism and the insulin resistance.