Background: Midkine (MK) is a heparin-binding growth factor, with a low molecular weight of 13 kDa. MK promotes reproduction, development, repair, survival, migration and other activities of target cells. MK expression by innate the human immune system antigen presenting cells, was suggested by a previous research work conducted in the Department of Microbiology and Immunology, College of Medicine and Health Sciences, Sultan Qaboos University (SQU). Aim: This study aims to investigate the production of MK by the antigen presenting cells (APCs) of the human innate immune system. Methods: Monocytes, macrophages, monocyte-derived dendritic cells (MDDCs), myeloid dendritic cells and plasmacytoid dendritic cells (pDCs) were obtained from peripheral blood mononuclear cells (PBMCs) of healthy individuals (n=3 for each) and then stimulated with Lipopolysaccharides (LPS), poly I:C, resiquimod, ODN and a combination of all ligands to assess the synergistic effect of different Toll Like Receptors (TLRs) in inducing MK production. Results: MK expression was detected at the mRNA level in all the investigated APCs, and at the protein level in monocytes, macrophages, MDDCs and pDCs only. No synergistic effects were observed for the production of MK upon stimulation with the different TLRs. Conclusion: MK is expressed by some innate APCs upon triggering through TLRs that use MyD88 and TRIF for their signaling. The expression of MK by these APCs suggests a role for MK in the regulation of the immune system and in cell proliferation and survival