Herba Agastache (HA), the dried ground part of Agastache rugosa O. Kuntze, has been shown to have antimicrobial and antitumor properties and can be used to treat infectious diseases including cold and flu. To elucidate the mechanism by which HA elicits pharmaceutical potencies, the effects of HA on nitric oxide (NO) and pro-inflammatory cytokine production in mouse peritoneal macrophages were determined. When HA extract was used in combination with recombinant interferon-${gamma}$ (rIFN-${gamma}$), a considerable increase in the NO production was observed, whereas HA alone generally had marginal effect on the NO level. The increased production of NO by rIFN-${gamma}$ plus HA was dose-dependently inhibited by $N^G$-monomethyl-L-arginine (L-NMMA) and L-$N^6$-(1-iminoethyl)-lysine (L-NIL), L-arginine analogues or pyrrolidine dithiocarbamate (PDTC), a nuclear factor-${kappa}B$ (NF-${kappa}B$) inhibitor. Treatment of rIFN-${gamma}$ plus HA in peritoneal macrophages resulted in an increased production of pro-inflammatory cytokines, such as tumor necrosis factor-${alpha}$ (TNF-${alpha}$), interleukin-$1{eta}$ (IL-$1{eta}$), and interleukin-6 (IL-6). However, the concentrations of these cytokines substantially decreased with the addition of PDTC. These findings illustrate that the antimicrobial and tumoricidal properties of HA, in combination with rIFN-${gamma}$, could be attributed to its ability in inducing macrophage activation, such as enhanced production of NO and pro-inflammatory cytokines via the NF-${kappa}B$ signaling pathway.