Studies over 10 yr have demonstrated local nasal immunotherapy (LNIT) to be an effective treatment for rhinitis due to pollens and mites. The aim of our work was to investigate the effects of LNIT on the local inflammatory phenomena, employing the model of nasal allergenic challenge, since no evidence has been yet provided about LNIT effects on the events due to allergic reactions. We evaluated, in addition, the possible effects of LNIT on some systemic immunologic parameters and its clinical efficacy. The study involved a double-blind, placebo-controlled trial of preseasonal immunotherapy with Parietaria in 20 adults. A significant reduction of symptoms, inflammatory infiltration, and intercellular adhesion molecule-1 (ICAM-1) expression on epithelial cells after nasal challenge was evidence as long-lasting effect. No changes in serum allergen-specific IgE, IgG, and soluble eosinophil cationic protein were detected, whereas an unexpected increase of soluble ICAM-1 was found in the placebo group only. The treatment was well tolerated and a significant clinical improvement under natural allergenic exposure was observed in the active group. The present study provides, for the first time, evidence that LNIT is able to modulate the nasal allergic inflammation.