Objectives The current research seeks to assess the anti-atherogenic activity of Egyptian artichoke leaf extract in hypercholesterolemic rats. Materials and methods Male albino rats were categorized into five groups; control group, high cholesterol diet treated group (HCD), HCD + low dose of artichoke, HCD + high dose of artichoke and HCD + Atorvastatin. Results Both doses of artichoke extract significantly decreased the concentration of serum cholesterol, triglycerides, and LDL-C in HCD rats as compared to that of their matching controls, p < .05. The treatment with artichoke led to the inhibition of the liver hydroxymethylglutaryl-CoA (HMG-CoA) reductase. Besides, the extract was proven to be cardioprotective effective by increasing antioxidant activity. The effect of the highest dose of artichoke was more apparent than the effect of the lowest one. The biochemical data was reinforced by the histopathological studies. Discussion and conclusion Artichoke may act as a natural source for the elimination of cardiovascular ailments.