Background/Aim: Natural mofettes are gases resulting from post-volcanic emanations. This study aimed to examine the effect of mofette therapy on plasma oxidative stress and antioxidant parameters in rats after experimental induction of myocardial ischemia, as well as on structural changes in myocardial tissue. Materials and Methods: White Wistar-Bratislava rats were divided into three groups. In groups 2 and 3, myocardial ischemia was induced by isoproterenol. Rats in group 3 were additionally exposed to high levels mofettes. Oxidative stress and antioxidant parameters were determined in plasma. The structural changes of the myocardium were observed in paraffin embedded slices contrasted using Goldner's trichrome staining. Results: A statistically significant change in serum oxidative stress biomarkers, including nitric oxide, malondialdehyde, total oxidant status, as well as in the tested antioxidant molecules and total antioxidant capacity were observed in group 3 compared to group 2. Also, rats of group 3 showed an obvious improvement in inflammatory infiltration and repair of necrotic areas through collagen proliferation (proliferation of fibrous connective tissue) compared to group 2. Conclusion: Mofette had a beneficial effect on the balance between oxidative stress and antioxidant status following experimentally induced myocardial ischemia. Natural mofettes are gases resulting from natural postvolcanic emanations (1) that are found in certain areas of Romania, e.g. in the Harghita volcanic massif, from which carbon dioxide, present in a 95-98% proportion, is used as a therapeutic factor (2, 3). Along with carbon dioxide, mofette gas contains small amounts of other volcanic emission gases: ammonium, sulfur, helium and radon (4, 5), which induce pulverization of CO 2 molecules, increasing the penetration power of CO 2 (1-3). Mofettes also contain positive and negative air ions, 2,000-15,000 ions/cm 3 , and have a radioactivity of 0.3 μCi/l, without cancer risk, and a radon concentration lower than 1% (4). In Romania, there are natural mofettes in the spa resorts Covasna,