Exocarpium Citrulli is the cortex of Fructus Citrulli. In Korean traditional medicine, it has been used to treat edema, dysuria, mouth and tongue sores. Although Exocarpium Citrulli has been known to possess anti-cancer activity, it has been rarely conducted to evaluate the anti-inflammatory activity. The present study was examined to evaluate the anti-inflammatory effects of the Exocarpium Gitrulli EtOH extracts (ECE) in vitro. Inflammatory mediators were detected after the addition of LPS with or without ECE in Raw 264.7 macrophage cell lines. LPS plays a key role in leading to the massive production of pro-inflammatory cytokines, such as TNF-a, 1L-1β and IL-6 in macrophages. In this study, cell viability assay (MTT assay) was conducted to determine the non-cytotoxic concentration of ECE. The dosages (0.1 and 0.3 mg/ml of ECE used in this study had no significant cytotoxicity during the experimental period. The relative level of NO was measured with Griess reagent. Pro-inflammatory cytokines were detected by EUSA assay. The cell was treated with 1 μg/ml of LPS 1 h before adding ECE. The level of NO and cytokines (TNF-a, IL-1β) in culture medium was increased by LPS application. However, these increases were attenuated by treatment with ECE.