Myocardial infarction (MI) is one of the leading causes of death worldwide. Oxidative stress and inflammation play vital role in the development of MI. The Indian basil or Tulsi (Ocimum sanctum Linn.), owing to its antioxidant potential, is used in the traditional system of Indian medicine to treat various disorders. We evaluated methanolic extract of O. sanctum (Tulsi) leaves on inflammation in isoproterenol (ISP) induced MI in rats. ISP-induced MI increased the levels of cardiac markers, phospholipases and phospholipid content. However, the same were reduced on pre-treatment with methanolic extract of O. sanctum leaves. The activities of 5-lipoxygenase and cycloxygenase-2 and levels of leukotriene B4 and thromboxane B2 were also elevated in ISP-treated rats, which were significantly decreased (P < 0.001) in extract pre-treated rats. The enhanced mRNA expressions of nuclear factor kappa-B, 5-lipoxygenase activating protein and receptor for leukotriene B4 on MI induction, were considerably reduced (P < 0.001) on extract pre-treatment. Histopathological analysis also confirmed the findings. The results also revealed the high phenolic content of methanolic extract of O. sanctum leaves. The study demonstrated that methanolic extract of Tulsi leaves can decrease inflammation in the cardiac tissue of ISP-induced MI in rats and its effect may be through downregulation of oxidative stress and arachidonic acid pathway. This cardioprotective effect may be due to the high phenolic content of methanolic extract of O. sanctum leaves.