Background: Atherosclerosis is one of the major causes of morbidity and mortality in the world. Antioxidants play a major role in prophylaxis and prevention of progression and complications of atherosclerosis. Objective: In this study, we are evaluating the antiatherosclerotic effect of two antioxidants such as astaxanthin and lycopene. Materials and Methods: After acclimatization, 24 male SD rats, 8–10 weeks old, 150 ± 10 g, maintained as per CPCSEA guidelines were divided into four groups of six rats each. Baseline values of weight lipid profile and 2‑Thiobarbituric Acid Reactive Substances (TBARS) assay were taken. All the rats were fed with high cholesterol diet (HCD). HCD only, HCD + atorvastatin (50 mg/kg), HCD + lycopene (50 mg/kg), and HCD + astaxanthin (50 mg/kg) were given to control, standard, lycopene, and astaxanthin groups, respectively, through oral gavage for 45 days. The rats were sacrificed at the end of the study, blood sample collected from aorta, and then aorta was dissected for histopathology. Results: The lipid profile showed lycopene and astaxanthin decreased total cholesterol, low‑density lipoprotein‑cholesterol (LDL‑C), very LDL‑C, and triglycerides and increased high‑density lipoprotein‑cholesterol level significantly (P < 0.05) compared to the control but less than atorvastatin. The TBARS value of lycopene was significantly lower compared to HCD and atorvastatin groups, whereas astaxanthin was significantly less than HCD group only. The histopathology showed only Type I lesions, no naked fatty streaks, few foam cells in lycopene, and astaxanthin groups compared to control where we observed Type II and III lesions, visible fatty streaks and many foam cells with intimal thickening in HCD group. Conclusion: In this study, lycopene and astaxanthin showed antioxidant, antihyperlipidemic, and antiatherosclerotic property. This warrants further study for including them in the treatment of atherosclerosis.
