We have studied the relationship and behavior of serum imunoglobulin E (IgE) level, peripheral mononuclear cell human leukocyte antigen DR (HLA-DR) expression and erythrocyte glutathione antioxidant pathway in a group of patients suffering reactive asthma. These patients were treated by three cycles with three ozone therapy different protocols. Ozone major autohemotherapy [MAHT] (each cycle of 15 sessions at doses of 4 and 8 mg) and ozone rectal insufflations [RI] (each cycle of 20 sessions at dose of 10 mg). IgE and HLA-DR decreased with the three types of treatments, while increments in Reduced glutathione, Glutathione peroxidase, Glutation reductase and Glutathione S-trasferase were achieved with all treatments. Lung function and symptom tests were markedly improved. However, in all parameters the best response was obtained in the order MAHT at 8mg better than MHAT at 4mg better than RI at 10mg. Before ozone treatment glutathione antioxidant parameters were under the reference normal values suggesting the occurrence of oxidative stress associated to the atopic asthma. This study demonstrates the effectiveness of ozone therapy in reducing IgE and inflammatory mediators along with the induction of antioxidant elements. The study raises the role of systemic ozone therapy in atopic asthma by means of the immunomodulatory and oxidative stress regulation properties of this therapy.