In order to explore the anti-inflammatory effect and its underlying mechanism of Senecio scandens,petroleum ether extract of S. scandens (PEESS) was used to treat the lipopolysaccharide (LPS)-induced RAW264.7 cell. The cell proliferation was detected by CCK-8,the secretion of NO was detected by Griess method,and the expression of inflammation-associated factors was 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 significantly inhibited the secretion of NO in LPS induced RAW264.7 cells by a concentration-dependent manner. Besides,the expression of IL-1β and IL-6 was significantly inhibited by PEESS in LPS induced RAW264.7 cells. Meanwhile,PEESS also significantly reduced the expression of p-NF-κB p65 and p-p44/p22 MAPK proteins. In conclusion,the above results indicated that 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 S. scandens in cuing some inflammatory disease of animals.