Interleukin (IL)-5 produced by allergen specific T cells is a major cytokine in the allergic inflammation such as allergic rhinitis (AR). To inhibit the production of IL-5, water-soluble chitosan (WSC)-based IL-5 antisense oligodeoxynucleotide (AS-ODN) complex was generated. WSC, a biocompatible cationic polymer, was used as a non-viral vector for the improvement of stability and transfection efficiency. After condensation IL-5 AS-ODN with WSC, the size, morphology and zeta potential analysis of IL-5 AS-ODN/WSC complexes were performed. The protective effect of complex was also observed against the enzymatic degradation. In vitro transfection efficiency into H1299 epithelial cells was investigated by flow cytometer and inhibition effect of IL-5 levels was also evaluated in D10.G4.1 cells. In the murine model with AR, the IL-5 and IgE levels closely related to the allergic inflammation were significantly reduced after the intranasal administration of IL-5 AS-ODN/WSC complexes. Based on these results, the condensation with WSC improved the physicochemical stability and transfection efficiency of IL-5 AS-ODN/WSC complex. Our results suggest that AS therapy using IL-5 AS-ODN/WSC complex can be an effective strategy in regulating IL-5 and may be applied to the treatment of allergic disorder related to IL-5.