Human secreted modular Ca²⁺-binding protein 1 (SMOC-1) is a matricellullar protein localized in the basement membrane of cells that generate it. SMOC-1 expression is upregulated in glomerular nephritis. However, its function in the cardiovascular system is almost unknown. The aim of the present study was to evaluate the function of SMOC-1 during inflammatory processes. We found that the RNA and protein levels of SMOC-1 were upregulated by inflammatory cytokines (interleukin-1b, transforming growth factor 1b (TGF-1 b) and tumor necrosis factor 1a). Moreover, stimulation of human monocyte derived macrophages as well as human umbilical vein endothelial cells (HUVEC) with anti-inflammatory lipids, nitro-oleic and nitro-linoleic acid, downregulated SMOC-1 RNA and protein levels. Furthermore laminar shear stress downregulated the expression level of SMOC-1 while hypoxia upregulated it. The presence of SMOC-1 in an endothelial cell derived extracellular matrix (ECM) potentiated the migration, but prevented adhesion of monocytes (THP-1 cells) and HUVEC. The Xenopus and Drosophila homologes of SMOC-1 have been reported to interact with Bone morphogenetic protein (BMP) signalling. Thus, we determined whether this is also the case for the human homologe. Co-expression of human SMOC-1 and BMP-response element luziferase-constructs in human embryonic kidney cells showed an attenuated luziferase signal. In conclusion, SMOC-1 is upregulated by inflammatory cytokines, such as TGF-1b, and acts then as a feedback regulator. Inhibition of BMP signalling favors matrix remodelling improving cell migration and effect that may explain the stimulation of inflammatory cell migration.