Several works are interested in studying the undesirable therapeutic effects of medicinal plants, which must be used with great caution because they can be toxic. Under this objective falls our work, which consists in studying the acute toxicity and anti-inflammatory action in vivo of the Essential Oil (EO) of the aerial part (seed) of Ferula sulcata Desf. harvested from the region of Setif in western Algeria. Two doses were applied by oral gavage (2000 and 5000 mg/kg body weight). After administration of the oil, the mice were continuously monitored for 14 days. The results obtained showed that there was no mortality or morbidity whereas the animals showed toxic effects e.g., behavioral and morphological changes. On the other hand, a significant increase (p<0.05) in body weight was observed. In addition, an important increase was recorded in the relative organ weights compared to the controls, whereas the liver was significantly increased (**p<0.05): 6.12±0.19; 6.14±0.31 in females compared to controls. Furthermore, ALT value decreased significantly (**p<0.05): 6.83±2.59 in males. In addition, the oral administration of EO at the dose of 600 mg/kg showed an interesting antiinflammatory activity comparable to indomethacin. Histopathological damage was observed in the liver and kidney tissues of mice treated with EO of this plant. Hence, the acute toxicity and anti-inflammatory activities of EO of F. sulcata Desf. are considered the first data.