Introduction: Senna occidentalis is a medicinal plant which is called “rai–rai” or “rai dorai” in Hausa. It is among the most commonly used plants that form the basis of primary healthcare for a majority of people living in rural and remote areas in Nigeria and other third world countries. Hyperlipidemia is a condition which is characterized by elevated levels of serum lipid profile. It is associated with many diseases such as atherosclerosis, cardiovascular diseases, and diabetes. Aims and Objectives: This study was aimed at assessing the effect of oral administration of aqueous leaf extract of S. occidentalis on serum lipid profile in rats. Materials and Methods: Phytochemical screening and effect of aqueous leaf extract of S. occidentalis on lipid profile was conducted. Thirty male albino rats were divided into six groups of 5 rats each. Group I was normal control, group II hyperlipidemic control, groups III, IV, and V were hyperlipidemic rats orally administered with 500 mg/kg, 250 mg/kg, and 166 mg/kg of aqueous leaf extract of S. occidentalis , respectively, for 4 weeks, and group VI were hyperlipidemic rats orally administered with 10 mg/kg of ruvastatin for 4 weeks. At the end of the fourth week, the animals were sacrificed and their serum total cholesterol (TC), triglycerides (TG), high density lipoprotein (HDL), and low density lipoprotein (LDL) levels were determined. Results: Results of phytochemical screening revealed the presence of tannins, saponins, cardiac glycosides, resins, and flavonoids. Significant ( P P S. occidentalis and those orally administered with 10 mg/kg of rosuvastatin when compared with group II. Rats orally administered with 250 mg/kg of the aqueous leaf extract were found to have significantly lower ( P Conclusion: It could be suggested that aqueous leaf extract of S. occidentalis at 500 mg/kg could cause antihyperlipidemic effect against dietary-induced hyperlipidemia.