Background: Flavonoids are a group of polyphenolic compounds with antioxidant properties that help reduce cardiovascular risk factors. Kelussia odoratissima is a flavonoid-containing plant, the effect of which was analyzed on decreasing blood lipid levels in mice. Objectives: The present study was carried out with the aim of determining the anti-hyperlipidemia effects of this herb on mice. Materials and Methods:In this preclinical study, 70 Balb/c mice were divided to five 14-member groups and received normal diet, normal diet containing 5% olive oil, high cholesterol (2% cholesterol and 5% olive oil) diet and high cholesterol diet accompanied by Kelussia odoratissima 10% or 20% hydro-alcoholic extract. After two weeks, blood samples were taken and cholesterol, triglyceride, low density lipoprotein (LDL), very low density lipoprotein (VLDL), high density lipoprotein (HDL), and fasting blood sugar (FBS) were measured. Results: In this animal model, the levels of all serum lipids including cholesterol, HDL, VLDL, LDL, triglyceride and FBS had a significant decrease two weeks after the beginning of the study. Moreover, at the same time, in the group that received 20% hydro-alcoholic extract, the serum levels of cholesterol, HDL and LDL had a significant decrease (P < 0.05). Conclusions: Kelussia odoratissima might have a desirable effect on serum lipid profile and might have beneficial effects on hyperlipidemic patients.