Curcumin, a lipid-soluble compound extracted from the plant Curcuma Longa, has been found to exertimmunomodulatory effects via macrophages. However, most studies focus on the low bioavailability issue ofcurcumin by nano and microparticles, and thus the role of macrophages in the anticancer mechanism of curcuminhas received little attention so far. We have previously shown the potential biocompatibility, biodegradabilityand anti-cancer effects of dendrosomal curcumin (DNC). In this study, twenty-seven BALB/c mice were equallydivided into control as well as 40 and 80 mg/kg groups of DNC to investigate the involvement of macrophagesin the antitumor effects of curcumin in a typical animal model of metastatic breast cancer. At the end ofintervention, the tumor volume and weight were significantly reduced in DNC groups compared to control(P<0.05). Histopathological data showed the presence of macrophages in tumor and spleen tissues. Real-timePCR results showed that DNC increased the expression of STAT4 and IL-12 genes in tumor and spleen tissues incomparison with control (P<0.05), referring to the high levels of M1 macrophages. Furthermore treatment withDNC decreased STAT3, IL-10 and arginase I gene expression (P<0.05), indicating low levels of M2 macrophage.The results confirm the role of macrophages in the protective effects of dendrosomal curcumin against metastaticbreast cancer in mice.