Triptolide, an active component purified from the medicinal plant Tripterygium wilfordii Hook F., is potent in anti-inflammation and immunosuppression. Dendritic cells (DC), one of important targets of immunosuppressants, play crucial roles in linking the innate immunity and adaptive immunity. However, the effects of triptolide on DC have not been fully elucidated. Chemoattraction of neutrophils and T cells by DC may favor their interactions and initiation of immune response. Here we demonstrate that triptolide significantly impairs DC-mediated chemoattraction of neutrophils and T cells both in vitro and in vivo by suppressing DC production of CC and CXC chemokines including MIP-1alpha, MIP-1beta, MCP-1, RANTES, TARC, and IP-10 in response to LPS. Furthermore, triptolide-mediated inhibition of NF-kappaB activation, Stat3 phosphorylation and increase of SOCS1 expression in DC may be involved in the inhibitory effect of triptolide. Our study provides a novel mechanistic explanation for the anti-inflammatory and immunosuppressive activities of triptolide.