Ocimum sanctum (OS) Linn.herb, commonly known as ‘Tulsi’ has been recommended for the treatment many disorders, because of its antioxidant, hypolipidemic, anti-inflammatory and various other pharmacologic effects. The present study was focussed on the effect of methanol extract of OS leaves (MOS), on the changes in lipid profile, activity of paraoxonase 1 (PON1) and mRNA expression of heart type fatty acid binding protein (H-FABP) in isoproterenol (ISP) induced cardiac damage. Rats were grouped as follows: 1) Control, 2) MOS (15mg/100g b.wt.), 3) ISP (10mg/100g b.wt.), 4) MOS(15mg/100g b.wt.) +ISP (10mg/100g b.wt.). MOS was administered every day for 30 days. ISP was administered at 29th and 30th day to induce myocardial damage. At the 31st day, all animals were sacrificed and various parameters were studied. ISP treatment caused a significant elevation in the activities of serum cardiac markers and reduction in the expression of H-FABP in heart tissue, which was reversed on MOS pretreatment. MOS pre-treatment also caused reduction in the infarct size in the myocardium after ISP induction. The serum and tissue lipid profiles were reduced, while the serum high density lipoprotein cholesterol was increased by the pre-treatment of MOS. The activity of cardioprotective enzyme PON1 was also increased on MOS pre-treatment. MOS administration caused a reduction in the activities of the enzymes HMG CoA reductase and phospholipases. Hence it can be concluded that MOS possesses significant hypolipidemic and cardioprotective effect.