Abstract Limonium duriusculum is used in folk medicine to treat inflammatory disorders and has gained attention due to its richness in apigenin. The present investigation was performed to evaluate and confirm its anti-inflammatory properties, in cell lines and animal models. The potential anti-inflammatory properties of n-butanol (n-BuOH) extract of L. duriusculum (BEL) and isolated apigenins were examined on NF-κB transcriptional activity in TNFα- or LPS-stimulated cells, and on in vivo acute inflammatory models (carrageenan induced paw edema and peritonitis). BEL treatment was able to inhibit the activity of an NF-κB reporter gene in HCT116 cells both in the absence and in the presence of exogenous TNFα, used as NF-κB pathway inducer. This anti-inflammatory effect was even more potent compared to Apigenin (APG1) and was confirmed using monocyte-derived THP-1 cells treated with LPS to stimulate NF-κB-dependent transcription of IL-6 and TNFα mRNAs. Apigenin7-O-β-(6''-methylglucuronide) (APG2) was instead inactive both in HCT116 and THP-1 cells. BEL (oral, 200 mg/kg) led to paw swelling inhibition, vascular permeability and peritoneal leukocyte and PN migration diminution. Apigenins (intraperitoneal, APG1, APG2: 20 mg/kg) also evoked a significant anti-edema effect, early vascular permeability and leukocyte influx reduction. Collectively, this study demonstrates for the first time the effectiveness of L. duriusculum to inhibit NF-κB-dependent transcriptional responses in HCT116 and THP-1 cells. In vivo studies also established that L. duriusculum possesses a potential anti-inflammatory effect, confirm its traditional, empirical use, that could be attributed to its richness in apigenin.