The effect of omeprazole (OPZ) suppository on rat rectal mucosa was investigated microscopically. The suppository was prepared with Witepsol H15 base by molding method. Rectal irritation was evaluated according to defined pathological features. The suppository produced a slight damage to the rectal mucosa at 1 hr after the interectal administration, which was almost completely recovered within 24 hr. The damage was not due to OPZ but due to suppository base, Witepsol H15, itself, since Witepsol H15 suppository without OPZ produced the same damage. Therefore, it was concluded that OPZ itself has no rectal mucosa-irritating effect and thus can be developed as a suppository dosage form without any further toxicity problems.