Purpose: The purpose of this study was to investigate the effects of Prunellae Spica Water Extract(PSE) on immune response in macrophage cells. Methods: We had devided two group the one is normal group; not treated with PSE, and the other is experimental group; treated with PSE. We measured the cell viability of PSE on RAW 264.7 cells and investigated production of nitric oxide(NO) and cytokines such as interleukin(IL)-$1{eta}$, IL-6 and tumor necrosis factor (TNF)-$alpha$ with sample PSE. Results: 1. Cell viability of PSE on RAW 264.7 cells was significantly decreased in both 24 hr and 48 hr incubation. 2. NO production of PSE on RAW 264.7 cells was significantly increased in both 24 hr and 48 hr incubation. 3. IL-$1{eta}$ production of PSE on RAW 264.7 cells was significantly increased under concentration over $50;{mu}g/m{ell}$ in 24 hr incubation. 4. IL-6 production of PSE on RAW 264.7 cells was significantly increased under concentration over $50;{mu}g/m{ell}$ in 24 hr incubation. 5. TNF-$alpha$ production of PSE on RAW 264.7 cells was significantly increased under concentration over $50;{mu}g/m{ell}$ in 24 hr incubation. Conclusion: NO, IL-$1{eta}$, IL-6 and TNF-$alpha$ production of PSE on RAW 264.7 cells was significantly increased. This study suggest that PSE stimulates the macrophage and enhances the immune response.