Abstract: Intranasal administration has the advantages of quick onset, high bioavailability, potential delivery into brain, and non-invasive. However, the limitations of the complex nasal microenvironment, such as the mucosal barrier, ciliary movement, low pH mucous layer, and enzyme degradation, appear to be key challenges in nasal drug development. Although a large number of animal trials provide reference data for the development of nasal drugs, the species differences, high cost and long cycle make this approach more difficult to develop, especially in the high-throughput preclinical screening stage of new drugs. Therefore, it is critical to select a nasal model with good in vitro and in vivo correlation for preclinical drug research. Whether the targeting through the nasal into the brain or blood, the epithelial cell barrier directly determines the bioavailability and efficacy during the intranasal administration. Moreover, mucosal irritation is also one of the critical evaluations of the safety aspects during nasal drugs development, where cell model can be quite useful. Therefore, this review summarized the application of the in vitro nasal model based on nasal epithelial cells in the nasal drug development.