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Objective: The purpose of this study was to examine the protective effects of Myrtus communis L. (MC) extract on high fat-diet (HFD) induced heart and aorta damage by evaluating oxidative stress and the endothelial nitric oxide system (eNOS). Materials and Methods: Wistar albino male rats were divided into 3 groups (n=7) as control, HFD, and HFD+MC. Rats in HFD and HFD+MC groups were HFD fed for 16 weeks and in the last 4 weeks saline or MC (100 mg/kg) was administered orally (5 days/week). Triglyceride, cholesterol, and high-density lipoprotein (HDL) were estimated in blood serum. Tissue oxidative stress and inflammatory parameters were evaluated biochemically. Tissue morphologies, eNOS, inducible NOS (iNOS), and NADPH oxidase-2 (NOX-2)-immunopositive and apoptotic cells were evaluated histologically. Results: Altered serum lipid profiles, degenerated heart, and aorta morphology, increased malondialdehyde, 8-hydroxy-2- deoxyguanosine, tumor necrosis factor-alpha, monocyte chemoattractant protein-1 and myeloperoxidase levels, and iNOS, NOX-2 immunopositive and apoptotic cells, decreased NO levels, eNOS-immunopositive cells in both tissues were observed in HFD group. All these parameters improved in the HFD+MC group. Conclusion: This study revealed that HFD-induced obesity increased iNOS activation and oxidative stress in the cardiac and aortic tissues of the rats. MC improved oxidant/antioxidant balance and prevented heart and aorta damage via eNOS involvement. [ABSTRACT FROM AUTHOR]