Background: Smilax corbularia is a Thai medicinal plant locally known as 'Hua-Khao-Yen Neua', which is used for treating inflammatory conditions. Objective: To evaluate the anti-inflammatory effect of S. corbularia extracts and its isolated compounds by determination of inhibitory effects on lipopolysaccharide-stimulated PGE2 release, and TNF-α and NO production from RAW 264.7 cells. Methods: The inhibitory effect of aqueous and ethanolic extracts of this plant were determined on LPS-induced NO production, TNF-α and PGE2 release in RAW 264.7 cells, as an in vitro indication of possible anti-inflammatory activity. The compounds from active extract were isolated by bioassay-guided fractionation. Results: Only the ethanolic extract of this plant inhibited TNF-α and NO production, with IC50 values of 61.97, and 83.90 μg/ml respectively. Three flavonols, engeletin, astilbin and quercetin were isolated from the ethanolic extract. quercetin possessed the highest inhibitory effect on NO production with IC50 11.2 μg/ml (37.1 μM), whereas engeletin and astilbin had no activity (IC50 >100 μg/ml). All three flavonols possessed potent inhibition of PGE2 release with IC50 values of 14.4, 19.6 and 19.9 μg/ml (33.2, 43.5 and 65.8 μM) respectively. Quercetin also exhibited the highest inhibitory effect on TNF-α production (IC50 = 1.25 μg/ml or 4.14 μM), but engeletin and astilbin had no activity. Conclusion: This is the first report of isolated compounds from S. corbularia with potential anti-inflammatory effects, and the results support the use of this plant by Thai traditional doctors for treatment of inflammatory diseases.