The purpose of the present study is to investigate the influence of gastric retention of ecabet sodium (ECS) on its mucoprotective effect in rat ulcer models. Mini-tablets containing 9 mg ECS were prepared using the direct compression method. The release rates of ECS mini-tablets were controlled by the amount and viscosity grade of hydroxypropylmethyl cellulose incorporated. Gastric retention of ECS mini-tablets after oral administration to rats was visually confirmed using a fluorescence imaging system. Because ECS mini-tablets exhibited size-dependent gastric retention, their gastric retention time was prolonged as the release rate decreased. In the in vivo efficacy study, gastro-retentive dosage forms of ECS did not influence the mucoprotective effect in the immediate irritation model but enhanced the effect in the delayed irritation model compared with ECS suspension. This finding indicates that the duration of the mucoprotective effect of ECS can be extended by the employment of gastro-retentive dosage formulations and provides a rationale for development of ECS gastro-retentive dosage forms.