Evaluation of oral mucosal irritation is required by regulatory agencies when the intended clinical route of the drug candidate is intraoral administration. In this study, we investigated whether it was possible to evaluate oral mucosal irritation in rats by an intraoral instillation which was thought to mimic the clinical route of gargle products. Although no oral mucosal irritation was observed in the animals instilled with 0.5% and 4% sodium dodecyl sulfate (SDS, an anionic detergent) solutions for 10 days, instillation of 15% SDS solution for 4 days induced oral mucosal irritation macro- and microscopically, and this was evaluated as moderate irritant. It was suggested that the oral mucosal irritation test by intraoral instillation in rats could be a simple and useful method mimicking the clinical route of gargle products.