Objectives : This study was carried out to investigate the anti-ulcer effects of Pyeongwibunsoeum extract and Misoprostol on indomethacin-induced gastric mucosal lesions of mice. Methods : Experimental groups were classified into non-treated group, non-administered group, Misoprostol-administered group and Pyeongwibunsoeum-extract-administered group. This study examined the morphological change, distribution of mast cells and apoptic cells, PNA reaction, COX-1, BrdU, NF-B p50, COX-2, IL-2R-, and ICAM-1of gastric mucosa. Results : 1. The hemorrhagic erosion of gastric mucosa was reduced in the Misoprostol-administered and Pyeongwibunsoeum-extract-administered groups. 2. The Misoprostol-administered group and Pyeongwibunsoeum-extract-administered group showed positive reaction on the PNA distribution. 3. The distribution of apoptic cells, activity of NF-B p50, COX-2, IL-2R-, and ICAM-1 decreased in both the Misoprostol-administered group and Pyeongwibunsoeum-extract-administered group. 4. The Misoprostol-administered and Pyeongwibunsoeum-extract-administered groups showed increase on COX-1, BrdU. Conclusions : As the results indicate, hemorrhagic erosion of gastric mucosa were reduced in both the Misoprostol-administeredand Pyeongwibunsoeum-extract-administered groups, and severe inflammatory reaction of gastric mucosa was reduced. The effects on the Pyeongwibunsoeum-extract-administered group were superior to those on the Misoprostol-administered group. Pyeongwibunsoeum extract can be widely administered for gastric ulcer disease in clinical treatments.