The aims of this study were to evaluate the anti-inflammatory activity and the possible anti-inflammatory mechanisms of Anastatica hierochuntica essential oil (EOAH). The essential oils were obtained by hydrodistillation of the aerial parts of the plant, and analyzed using gas chromatography and mass spectrometry (GC/MS). Their anti-inflammatory activity was evaluated using classical model of inflammation (carrageenan-induced paw edema and peritonitis). Nitric oxide radical-scavenging activity and lipid peroxidation were determined to assess the antioxidant activity of the essential oil. The EOAH mainly comprised Cuminaldehyde (33.8%), trans-Î²-Caryophyllene (32.5%), and Linalool (8.2%). EOAH significantly reduced edema, peritonitis, myeloperoxidase activity, and NOx-peritoneal lavage concentration induced by carrageenan. In addition, nitric oxide radical generated from sodium nitroprusside was significantly inhibited by the essential oil. Furthermore, EOAH was able to prevent Fe+2- or Fe+2 plus H2O2-induced lipid peroxidation. In conclusion, the EOAH exerts anti-inflammatory activity that could be related to its antioxidant capacity.