Recombinant human erythropoietin (rhEPO) is an effective treatment for myocardial infarction (MI) by promoting cardiac repair. However, additional investigations are required to determine its therapeutic value. The present study aims to investigate the effect of rhEPO in isoproterenol- (ISO-) induced myocardial infarction in Wistar rats. The efficacy of EPO pre- and post-therapy, as evaluated by histology, histomorphometry, and immunohistochemistry analysis, forms the novelty of the present study. Adult male Wistar Albino rats were taken in four groups (Group1- control, Group2 - ISO induced MI, Group 3-ten days rhEPO pre-treatment + ISO induction, and Group4-ISO induction + single dose rhEPO post-treatment), respectively. While Group 1 rats served as normal controls, Group 2 rats received a single ISO-isoproterenol (75 mg/kg b.w) on the final day of the trial. The rats in Group 3 received rhEPO (5000 IU/kg i.p) injections once daily for 10 days and a single dosage of isoproterenol (75 mg/kg i.p) on the 10th day. The group 4 rats received a single injection of ISO (75 mg/kg i.p.) followed by a single injection of rhEPO (5000 IU/kg i.p.) at a 2-hour interval. The rats were sacrificed, and samples were taken for further study. The therapeutic potential of rhEPO, i.e., ten days' pre-treatment before ISO induction, as well as the efficacy of a single dose of rhEPO post-treatment following ISO-induced myocardial damage, was investigated by immunohistochemical alterations of collagen, caspase1, p-SMAD3, and ASC proteins in the heart tissue. The histo pathological changes were evaluated in the heart tissues of study group rats. The immuno histo chemistry modifications reveal that erythropoietin post-therapy is more effective than pre-treatment against MI. However, histological abnormalities in cardiac tissues confirm it. As a result, rhEPO is more effective against MI after treatment than before treatment.