In the recently, increased concern has been focused on the pharmacology and clinical utility of herbal extracts and derivatives as a drug or adjunct to chemotherapy and immunotherapy. Here we investigated the modulatory effects of the extract of Zanthoxyli Pericarpium (ZP) in production of inflammatory mediators from Raw264.7 cells and expression of CD86, CD14, toll-like receptor (TLR)-4 from peritoneal macrophage. ZP enhanced the production of NO and $TNF-{alpha}$ as well as mRNA expression of iNOS and $TNF-{alpha}$. Treatment of peritoneal macrophage with ZP resulted in the enhanced cell-surface molecules expression of CD86, CD14 and TLR4. We assayed the effect of ZP in cell proliferation and production of $IFN-{gamma},;TNF-{alpha}$. ZP increased Con A-induced cell proliferation and production of $IFN-{gamma},;TNF-{alpha}$. These studies indicate that ZP induces macrophage activation and suggest the possible use of ZP in macrophage-based immunotherapies