Fermented milk is one of the best-known foods in terms of activating the host immune system; however, there are no reports regarding whether activation of the immune system depends on bacterial cells or cultured products that contain peptides, exopolysaccharides, and short-chain fatty acids, etc. In this study, J774.1 macrophage cells were stimulated by bacterial cells or cultured products prepared from milk fermented by L. delbrueckii subsp. bulgaricus isolated from Matsoni. We measured the concentrations of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in the culture supernatant. The production of TNF-α and IL-6 from J774.1 cells stimulated by bacterial cells or cultured products was higher than that stimulated by skim milk. Furthermore, the production of IL-6 from J774.1 cells stimulated by cultured products was significantly (p<0.05) higher than that stimulated by bacterial cells. These data suggest that macrophage activation in fermented milk depends more strongly on cultured products than bacterial cells.