OC-108 is a novel sclerosing agent for hemorrhoids, containing aluminum potassium sulfate (alum) and tannic acid as its main ingredients. In clinical studies, OC-108 injection therapy for severe internal hemorrhoids proved to be highly effective, not only on bleeding but also for prolapse, and the effects were comparable to hemorrhoidectomy. The aim of this study was to elucidate the mode of action by administrating the agent s.c. to mice and rats. In response to OC-108 injection, inflammation with necrosis developed at an early stage followed by granuloma formation with fibrosis at the injection site. Necrotic debris with aluminum was observed in the granuloma for a long period. Alum, as well as OC-108, induced vascular permeability, leukocyte infiltration, and granuloma formation; however, tannic acid did not. On the other hand, tannic acid inhibited leukocyte infiltration induced by alum but did not inhibit granuloma formation. These results indicate that OC-108 causes sclerosis and retraction of hemorrhoids through fibrosis associated with granulomatous chronic inflammation induced by the main active ingredient alum and that the adjunct ingredient tannic acid reduces excessive acute inflammation induced by alum.