© Copyright 2018 by Gazi University Medical Faculty.Objective: Ischemia-reperfusion injury is a chain of events put in place by tissue ischemia. Reperfusion following the damage of cell causes an active inflammatory response. In our research we tried to evaluate the protective effect of Levosimendan and Nigella Sativa on myocardial ischemia-reperfusion injury in rats. Methods: We included twenty-four Wistar albino rats in our research. The rats were randomly divided into four experimental groups. The coronary arteries of rats in Group C (control group) were not occluded or reperfused. Left anterior descending coronary artery was ligated for 30 min to perform myocardial IR and then reperfused for 2 h in the IR (IR), IR-Levosimendan (24μg/kg) (IRL) and IR-Nigella Sativa (0.2 mL/kg) (IRNS) group. Results: Inflammation findings were significantly higher in the IR group compared with the C, IR-NS, and IR-L groups (p=0.001, p=0.019, p=0.019, respectively). Compared with the C, IR-NS, and IR-L groups, the microscopic myocardial disorganization was significantly higher among the IR group (p<0.0001, p=0.007, p=0.001, respectively). The light microscopic myocardial tissue interstitial fibrosis levels were significantly higher in the IR group than in the C, IR-NS, and IR-L groups (p<0.0001, p=0.044, p=0.003, respectively). Conclusion: Levosimendan and NS administration at the beginning of myocardial ischemia can provide varying degrees of protection against negative effects of variations in light microscopic inflammation findings, myocardial disorganization degrees and myocardial tissue interstitial fibrosis levels.