Objective: To investigate the effect of lycopene on lipoprotein metabolism during D-galactosamine/lipopolysaccharide (D-Gal/LPS) induced hepatitis in experimental rats. Methods: The efficacy of lycopene was validated during D-Gal/LPS induced hepatitis by analyzing the activity of lipid metabolizing enzymes such as lipoprotein lipase (LPL), lecithin- cholesterol acyl transferase (LCAT) and hepatic triglyceride lipase (HTGL). Lipo protein analyses were done by the estimation of very low density lipoprotein cholesterol (VLDL), low density lipoprotein cholesterol (LDL) and high density lipoprotein cholesterol (HDL). Results: The toxic insult of D-galactosamine/lipopolysaccharide (D-Gal/LPS) in experimental group of animals reduces the normal values of lipid metabolizing enzymes due to liver injury. The significant drop in the levels of HDL and concomitant increase in the values of VLDL and LDL were observed. The pretreatment of lycopene restore these altered values to near normal level in experimental group of animals. Conclusions: In the light of results, it can be concluded that administration lycopene stabilizes the lipoprotein levels by regulating the lipid metabolizing enzymes through its antioxidant defense and helps to maintain the normal lipid metabolism during toxic injury in liver.