The non-sedating third generation antihistamine levocetirizine has ample evidence of efficacy in allergic rhinitis. In vitro studies suggested that levocetirizine has anti-inflammatory properties not simply related to the antihistamine activity but also to regulation of eosinophils. We performed a double-blind placebo-controlled study in 40 children allergic to house dust mites with persistent rhinitis with the primary aim to evaluate the anti-inflammatory efficacy of levocetirizine measuring eosinophil-related parameters and exhaled nitric oxide (eNO). After one month of treatment, a significant improvement in nasal symptom-medication scores was observed in actively but not in placebo treated patients. After 3 months of treatment, a significant effect was detected on eosinophilic cationic protein (ECP) in nasal mucosa and on nasal eNO in active treated patients. This suggests that during treatment of mite-allergic children with levocetirizine the early improvement in nasal symptoms is due to the antihistamine activity, while more time is needed to achieve an effect on allergic inflammation.