Oral ulcer is a lesion with multifactorial causes and occurs worldwide. The lesion usually resolved within 14 days, but the pain may have an impact on the quality of patient’s life. Therefore, having a natural derived remedy that can reduce healing time would be a great advantage. This study aims to investigate histological sections of buccal ulcer on rats treated with aqueous extract of Piper sarmentosum (AEPS).Glacial acetic acid was used to induce buccal ulcer on male Sprague Dawley rats. Control group received normal saline while the experimental group received AEPS for treatment. On certain days of post-ulcer induction, buccal ulcer tissue samples were harvested, sectioned and stained with Hematoxylin and Eosin (H&E). Histological slides were examined for inflammation and scored. The inflammation severity reduced from day 2 to day 12. In the experimental group there was a statistically significant differences of inflammation score, particularly on day 2 with a score of (2.8 + 0.2). Neutrophils were less in the experimental group and the tissue debris clearance was faster compared to control group. Full reepithelization was observed on both treated tissue sections on day 12 with less severe inflammation. Topical application of AEPS is proven to have anti-inflammatory effect by reducing the number of neutrophils during inflammation phase of oral ulcer healing