As the incidence of infectious diseases rapidly increases, interest in immunomodulators is increasing. Immunomodulators refer to natural molecules and biologically synthesized substances that have the ability to regulate the immune response of the innate and adaptive immune systems. Cirsium japonicum var. maackii (CJM) has been reported to have anti-oxidant, anti-diabetic, and anti-inflammatory effects. Notably, considering recent findings of tumor suppressive effect, CJM is expected to be effective in improving the immune system. In this present study, we confirmed immune-enhancing activity of flavone (i.e. cirsimarin, cirsimaritin, pectolinarin, pectolinarigenin, hispidulin) derived from CJM on interferon-gamma-induced RAW264.7 macrophages. In ELISA analysis, the expression of tumor necrosis factor-alpha and interleukin-6 in the cirsimarin and cirsimaritin groups was significantly increased compared to the normal group. In western blot analysis, the expression of cyclooxygenase-2 and inducible nitric oxide synthase in the cirsimarin and cirsimaritin groups was significantly increased compared to the normal group. Taken together, cirsimarin and cirsimaritin showed an immune enhancement effect by increasing cytokines and proteins related to the immune-boosting. Therefore, among flavones derived from CJM, cirsimarin and cirsimaritin are considered to be able to be used as functional food materials that are effective in enhancing immunity.