Effect of Boerhaavia diffusa extract on the Cell Mediated Immune (CMI) response in metastatic condition was studied using C57BL/6 mice model. Administration of Boerhaavia diffusa enhanced Natural Killer (NK) cell activity, antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent complement mediated cytotoxicity (ACC) and the activity was observed in treated group much earlier compared to the metastatic tumor bearing control. Production of the cytokine IL-2 was significantly enhanced by the administration of Boerhaavia diffusa compared to the untreated metastatic tumor bearing control. Levels of GM-CSF and pro-inflammatory cytokines such as IL-1beta, IL-6 and TNF-a were significantly lowered by Boerhaavia diffusa administration compared to metastatic control. The gene expression level of IL-2, IL-1beta, IL-6, TNF-alpha and GM-CSF in B16F-10 cells also correlate the above result. These results indicate Boerhaavia diffusa could enhance the immune response against metastatic progression of B16F-10 melanoma cells in mice.