Introduction: One of the greatest risk factors for cardiovascular diseases is hypercholesterolemia. Moringa oleifera is a good source of phytochemicals and is well explored for its antioxidant properties. Methods: The main aim of the present study was to assess the potential cholesterol lowering effect of Moringa oleifera leaf polyphenols (MOP) in an animal model. Five groups of male Wister rats were fed for 45 days as follows: a standard diet (GI); high fat-cholesterol diet (GII); high fat-cholesterol with MOP (100 and 200mg/kg body wt GIII & GIV respectively); and high fat-cholesterol with statins (Atorvastatin) (G-V). Results: Administration of MOP rich extract (GII and GIV) significantly (p=0.05) lowered the serum cholesterol, triglycerides and low-density lipoprotein cholesterol. A significant (p=0.05) decrease in the activity of the HMG CoA reductase enzyme was observed in GIII, GIV and GV but not in GI & GII. Conclusion: The results demonstrate that the polyphenol extract of Moringa oleifera leaves has a significant cholesterol lowering effect through inhibiting HMG CoA reductase activity and faecal bile acid binding.