Background: Human amnion mesenchymal cells (hAMCs), isolated from the amniotic membrane of human placenta, are a unique population of mesenchymal stem cells. Recent studies demonstrated that hAMCs could inhibit the activities and functions of several immune cells. However, their effect on inflammatory macrophages is largely unknown. This study investigated the effect of hAMCs on expression of inflammatory cytokines and mitogen-activated protein kinases (MAPKs)/NF-kappa B pathway in human THP-1 macrophages induced by lipopolysaccharide (LPS). Results: The levels of TNF-alpha and IL-1 beta secreted by LPS-stimulated THP-1 cells were increased significantly compared with those in the control group. After co-culture with different numbers of hAMCs, the levels of TNF-alpha and IL-1 beta in LPS-stimulated THP-1 cells were significantly reduced compared with the LPS group. The mRNA expression of TNF-a and IL-1 beta were also markedly inhibited. Moreover, treating LPS-stimulated THP-1 cells with hAMCs supernatants could also suppress TNF-alpha and IL-1 beta production in THP-1 cells. Important signaling pathways involved in the production of TNF-alpha and IL-1 beta were affected by hAMCs co-culture: hAMCs remarkably suppressed NF-kappa B activation and down-regulated the phosphorylation of ERK and JNK in LPS-stimulated THP-1 cells. Conclusions: Human amnion mesenchymal cells inhibited the production of TNF-alpha and IL-1 beta secreted by LPS-stimulated THP-1 cells, partly through the suppression of NF-kappa B activation and ERK and JNK phosphorylation.