The present study was undertaken to explore the interaction of garlic homogenate (GH) with propranolol (PRO) on ischemia-reperfusion injury (IRI) in isolated rat heart preparation. Albino rats were treated with GH at three different doses of 125 mg/kg, (GH-125), 250 mg/kg (GH-250) and 500 mg/kg (GH-500) for 30 days orally. The hearts were excised and mounted on modified Langendorff setup and subjected to 15 min global no flow ischemia and reperfused for 15 min. Pretreatment of animals with PRO, GH-125 and GH-250 (either alone or in combination) provided significant protection to myocardium from IRI damage as indicated by significant decrease in LDH and CK-MB activities in perfusate and an increase in activities of these enzymes in heart tissue homogenate. Similarly, the recovery (%) in developed tension and heart rate were significantly more in treated groups during post-ischemia when compared to control. Moreover, GH-250 either alone or with PRO showed significant increase in activities of antioxidant enzymes such as superoxide dismutase and catalase during IRI damage. However, GH-500 failed to show cardioprotective effect when given alone or along with PRO. These biochemical findings were supported by changes in histopathological studies.