Th2 immune cells infiltration into nasal mucosa is one of the characters of allergic rhinitis (AR). We aimed to explore whether inhibition of Th2 immune cells infiltration would attenuate AR progression. AR mouse model was established by i.p. injection of ovalbumin (OVA). The infiltrated immune cells into nasal lavage fluid were detected by flow cytometry. Cytokine concentration in serum was determined by ELISA. AR mice symptoms were indicated by the number of sneezing and nasal rubbing events. In AR mice, CCL2 expression levels and CD45CD11bLy6C inflammatory monocytes cells significantly increased as compared with control mice. CCL2 siRNA encapsulated nanoparticles (NP) prevent CCL2 expression and inflammatory monocytes infiltration in AR mice. NP treatment dramatically decreased the number of sneezing and nasal rubbing events in AR mice. Moreover, NP treatment attenuated serum OVA-specific IgE, OVA-specific IgG1 and histamine levels. Mechanically, NP treatment attenuates AR symptoms inhibiting Th2 cytokine (IL-4, IL-5 and IL-13) production. Nanomedicine-mediated prevention of inflammatory monocytes infiltration ameliorates ovalbumin-induced allergic rhinitis in mouse model.