Abstract: Background and Objective: Hypercholesterolemia is a risk factor for many cardiac and hepatic disorders. Visnagin (VIS) is a coumarin with an anti-inflammatory effect; however, its anti-dyslipidemia activity has not been investigated. This study evaluated the effect of VIS on hypercholesterolemia, oxidative stress and inflammatory response in high cholesterol diet (HCD)-fed rats. Materials and Methods: Rats received an HCD and VIS (30 and 60 mg kg–1) for 10 weeks and samples were harvested. Results: HCD increased serum cholesterol, triglycerides, LDL, VLDL, transaminases, CK-MB and pro-inflammatory cytokines and decreased HDL-cholesterol. VIS ameliorated serum lipids, liver and heart functions and cardiovascular risk indices in HCD-fed rats. Besides, VIS suppressed hepatic lipid peroxidation and increased the levels of cellular antioxidants. The effects of VIS were associated with increased hepatic LDL receptor (LDLR) and decreased HMG-CoA reductase (HMGR) expression. Conclusion: These results demonstrate the anti-hypercholesterolemic activity of VIS in rats. VIS ameliorated serum lipids, inflammation, liver and heart function and oxidative stress and modulated hepatic HMGR and LDLR. Therefore, VIS is a promising candidate for the treatment of hypercholesterolemia.