in order to explore the anti-inflammatory effect and underlying mechanism of Senecio scandens, Petroleum ether extract of Senecio scandens(PEESS)was used to treat the lipopolysaccharide(LPS)-induced inflammation response in mouse mononuclear macrophages RAW264.7. The cell proliferation were detected by CCK-8, and the secretion of NO were detected by Griess method, and the expression of inflammation-associated factors were detected by RT-PCR and Western blot. The results showed that PEESS at 0~80 μg/mL had no significant effect on the proliferation of RAW264.7. However, it can significantly inhibit the secretion of NO in LPS induced RAW264.7 cells by a concentration-dependent manner. And the expression of IL-1β and IL-6 were significantly inhibited by PEESS in LPS induced RAW264.7 cells. Meanwhile, PEESS also significantly reduced the level of p-NF-κB p65 and p-p44/p22 MAPK proteins. In conclusion, PEESS may participate in the process of anti-inflammatory response by inhibiting the expression of some pro-inflammatory mediators such as NO, IL-1β and IL-6, and the activation of the NF-κB and MAPK signaling pathways. This study lays a foundation for the application of Senecio scandens in cuing some inflammatory disease of animals.