Monocytes are key players in the induction of an immune response. Within the context of this study, we investigated the activa¬tion of toll-like receptors, mitogen activated protein kinases and NF-κB signaling in isolated human primary monocytes in response to low doses (0.05 and 0.1 Gy) and a high dose (1 Gy) of ionizing radiation. Using quantita¬tive RT-PCR and ELISA techniques, our results showed a positive regulation of TLR signaling in response to low doses but a less significant response at high doses. This activa¬tion was demonstrated via the activation of TLR signaling molecules. Furthermore, and in contrast to the high dose, the low doses showed increased phosphorylation levels of the protein IκBα, and therefore positive signaling of the NF-κB pathway. This result denotes pro-survival and pro-inflammatory responses. Additionally, MAPKs were activated in response to 0.05 Gy, while 0.1 and 1 Gy showed a downregulatory trend that may be related to activation of the PF4 gene. On the other hand, there was highly significant involvement of activated p53 and damaged genes in response to high but not low doses.