Objective：To investigate the effect of osthole on lipopolysaccharide (LPS)-induced inflammatory response in Caco2 cells and the underlying mechanism. Methods：Caco2 cells were treated with various concentrations of osthole prior to LPS treatment. The mRNA levels of interleukin (IL)-1β，IL-6 and TNF-α were detected by real-time PCR. Cells were treated with PKA inhibitors H89 or KT5720 prior to LPS at indicated doses to observe the effect of cAMP/PKA signaling pathway on osthole. The phosphorylations of p38，Erk and JNK were detected by Western blot. Results：The expressions of inflammatory factors IL-1β，IL-6 and TNF-α in Caco2 cells were significantly increased by LPS stimulation. Pretreatment of osthole significantly suppressed the up-regulation of inflammatory cytokines induced by LPS. PKA inhibitors failed to reverse the inhibitory effect of osthole. LPS induced significant phosphorylation of p38，Erk，and JNK in Caco2 cells，which were suppressed partly by osthole. Conclusion：Osthole attenuates LPS-induced nflammatory response in Caco2 cells. The inhibitory effect of osthole is independent on cAMP/PKA pathway. Osthole-induced reduction of phosphorylation of p38，Erk，and JNK may mediate its anti-inflammation action in Caco2 cells.