Cardiotoxicity is a frequent and severe side effect of 5-Fluorouracil (5-FU) chemotherapy, limiting its clinical use despite being one of the most potent anticancer agents. The present study was designed to evaluate the cardioprotective effect of a phenolic acid namely 2-pyrocatechuic acid (2,3 dihyroxybenzoic acid) against 5-FU induced cardiotoxicity in Wistar rats. Exposure to 5-FU at a dose of 20 mg/kg caused significant increase in serum cardiac biomarkers such as lactate dehydrogenase (LDH)), creatine kinase (CK), creatine kinase isoenzyme MB (CK-MB) activities, cardiac CK-MB index along as well as cTnI levels along with severe histopathological changes in cardiac tissues of rats indicating severe cardiotoxicity. Co-administration of 2- pyrocatechuic acid (2-PCA) with 5-FU at 3, 10, 30 and 100 mg/kg b.w./day for 14 days resulted in an amelioration of altered serum parameters in a dose dependent manner. Moreover, 2-PCA attenuated the cardiac tissue damage produced by 5-FU. The results indicated the potential of 2-PCA as a cardioprotective agent for the prevention and amelioration of 5-FU induced cardiotoxicity.