Two new T cell subsets may be involved in allergic rhinitis (AR) pathogenesis: Th17 and T regulatory cells, mainly producing IL-17 and TGF-beta respectively. Successful Sublingual Immunotherapy (SLIT) induces relevant immunological changes, thus the aim of this study was to evaluate serum IL-17 and TGF-beta levels in AR patients treated with SLIT for 2 years. Patients' blood samples were collected before initiating SLIT (baseline), three months after the end of the first pre-seasonal SLIT course, and at the end of the second pre-seasonal course. IL-17 was detectable only in the most severe allergic patients. SLIT significantly induced an increase in serum TGF-beta levels. There was moreover a significant relationship between TGF-beta and symptom severity and drug use at the end of the study. Therefore, this study provides clinically relevant evidence that two pre-seasonal SLIT courses may significantly affect serum TGF-beta levels.