Orai1 is the pore-forming subunit of the Ca(2+) release-activated Ca(2+) channels and plays a key role in the store-operated Ca(2+) entry. However, little is known about the function of this pathway in allergic rhinitis (AR). In this study, we examined whether the intervention of Orai1 pathway was capable of controlling IgE-mediated allergic reactions by using AR mice models.We used Western blotting and real-time reverse transcription polymerase chain reaction to evaluate Orai1 expression in nasal mucosa and nasal-associated lymphoid tissue (NALT) of normal, control, and 2-aminoethoxydiphenyl borate (2-APB)-treated mice. In addition, we analyzed concentrations of nasal lavage fluid leukotriene C4 (LTC4), eosinophil cation protein (ECP), ovalbumin-specific IgE, and interleukin-4 (IL-4) through enzyme-linked immunosorbent assay and measured messenger RNA (mRNA) levels of LTC4 synthase and ECP in nasal mucosa, and germline Cɛ transcription and IL-4 mRNA in NALT by using real-time reverse transcription polymerase chain reaction among groups.2-Aminoethoxydiphenyl borate administration into the nostril reduced numbers of sneezing and nasal rubbing as well as counts of invasive eosinophils in treated mice compared with those in control ones. Furthermore, the administration suppressed Orai1 expression in nasal mucosa and NALT of treated mice compared with that of control ones. Similarly, 2-APB treatment restrained nasal lavage fluid LTC4, ECP, ovalbumin-specific IgE, and IL-4 and their corresponding mRNAs in the previously mentioned tissues of treated mice in comparison with those of control ones.Our results indicate that 2-APB treatment effectively alleviates murine AR through pleiotropic activities.