Betulinic acid (BA), a pentacyclic triterpene isolated from Lycopus lucidus, has been reported to be a selective inducer of apoptosis in various human cancer and shown anti-inflammatory and immunomodulatory properties. We postulated that BA modulates the immunomodulatory properties at least two groups of protein mediators of inflammation, interlukin-1$eta$ (IL-1$eta$) and the tumor necrosis factor- $alpha$ (TNF-$alpha$) on the basis of the critical role of the monocytes and tissue macrophages in inflammatory and immune responses. TNF-$alpha$ and IL-1$eta$ were produced by BA in a dose dependent manner at concentration of 0.625 and 10 $mu$g/mL. The production of NO associated with iNOS was inhibited when treated with LPS at the concentration of 2.5 to 20 $mu$g/mL of BA whereas COX-2 expression was decreased at 2.5 to 20 $mu$g/mL. These modulations of inflammatory mediators were examined in LPS-stimulated RAW 264.7 cells and peritoneal macrophages. The morphology of macrophage was also examined and enhanced surface CD 40 molecule was expressed when treated BA at 0.625∼5 $mu$g/mL with or without LPS. Furthermore, BA (20 $mu$g/mL) enhanced apoptosis by producing DNA ladder in the RAW 264.7 cells. Our results indicated that BA induced activation of macrophage and pro-inflammatory cytokines. This may provide a molecular basis for the ability of BA to mediate macrophage, suppress inflammation, and modulate the immune response.