This work aimed to study the effects of gamma (g) irradiation on the total phenols and total flavonoid contents of celery leaves and to investigate effect of g-irradiated celery leaves powder (g-Irr.CLP) against hypercholesterolemia in rats. Results obtained that g-irradiation increased the amount of total phenolic and total flavonoid contents of dried celery. The results of biological study showed marked increases in the concentrations of serum lipid contents, activities of liver and cardiac marker enzymes and level of TBARS with a significant decrease in serum high-density lipoprotein concentration and reduction in the activities of anti-oxidant enzymes and glutathione contents of serum and heart tissues of hypercholesterolemic rats compared to control rats. Treatment of hypercholesterolemic rats with raw CLP or g-Irr.CLP showed significantly less severe damage and remarkable improvement in all of the measured parameters when compared to hypercholesterolemic rats lowered the concentrations of serum lipid contents, liver and cardiac marker enzymes and TBARS level and ameliorate anti-oxidant enzymatic status in serum and cardiac tissue. These results suggest that, treatment with g-Irr.CLP has a powerful modulating effect on hypercholesterolemia induced oxidative stress and has the potential in reducing cardiovascular complications.