Previously we have shown that perorally administered silymarin, a mixture of flavonolignans extracted from the seeds of Silybum marianum, possesses a hypocholesterolemic effect in rats fed high cholesterol diet enriched with fat. The aim of this paper was to complete the data concerning peroral and parenteral administration of silymarin. The rats fed standard laboratory diet did not respond to peroral administration of silymarin by decrease of serum cholesterol, but the mild increase in HDL cholesterol was found. Parenterally injected silymarin failed to reduce serum cholesterol both in rats fed high cholesterol diet and standard laboratory diet. The results suggest that silymarin could act either due to the fat-mediated improved bioavailability and/or by inhibiting of resorption of dietary cholesterol.