The use of herbs with medicinal value and biomedical effects has increased tremendously in the last years. However, inadequate basic knowledge of their mode of action is the main issue related to phytotherapy, although they have shown promising potential. To provide insights into these important issues, we tested here on appropriate in vitro models the efficacy of Angelica archangelica essential oil (Aa-EO) for anti-inflammatory properties. The results demonstrated that Aa-EO induced significant apoptosis and necrosis at high doses in U937 cells. We used nontoxic concentrations to treat for anti-inflammatory capacity. The results also demonstrated a decreased proinflammatory cytokine interleukin-6 level in human umbilical vein endothelial cells, as senescence in vitro model, when cells are challenged with lipopolysaccharide (LPS), one of the most powerful proinflammatory inducer in the presence of Aa-EO. In addition, down expression of miR-126 and miR-146a (inflammamirs) produced by LPS stimulation was reverted by Aa-EO simultaneous treatment. These results provide noteworthy basis for the development/formulation of new drugs for future clinical uses and new food products or dietary supplements for contrasting inflammation.