Abstract Aronia, a healthy fruit well known as black chokeberry, has health-promoting effects on hypertension, oxidative stress, and diabetes. Despite many reports of bioactivities of aronia, there is little scientific research on the potential for immune-enhancement. So, anthocyanin-fucoidan nanocomplex (AFNC, a nanocomplex of aronia extract and fucoidan) has been developed to improve immune-enhancement. This study aimed to identify immunomodulatory effects and underlying mechanisms of AFNC using RAW264.7 macrophages and cyclophosphamide-induced immunosuppressed mice. As a result, AFNC-treated RAW264.7 macrophages elevated the production of IL-2, IL-6, tumor necrosis factor (TNF)-α, and nitric oxide (NO). AFNC-enhanced inducible NO synthase expression via nuclear factor-κB signaling pathways. AFNC dosedependently increased levels of IL-2, IL-6, TNF-α, IL-10, IL-12, interferon-γ, or IL-4 in the serum and spleen of immunosuppressed mice. Taken together, AFNC encourages the immune-enhancing activity through immunostimulatory cytokine production by activation of macrophage. Therefore, these results suggest that AFNC is useful for immunodeficiency-related disorders. Practical applications In these days of prevalence of infectious diseases, individual immunity is very important. AFNC has the immune-enhancing effects through immunostimulatory cytokine production by activation of macrophage. Therefore, AFNC could be widely applied to ameliorate a variety of diseases caused by immunosuppression such as infectious diseases. KEYWORDS AFNC, cytokines, immunosuppressed mice, macrophages, nitric oxide, nuclear factor-κB