Syndecans (SDC) are important multifunctional components of the extracellular matrix mainly described in endothelial cells. We studied the expression and regulation of SDC in cultured MIN6B1 cells and pancreatic islets. qRT-PCR revealed that syndecan-4 (SDC4) was the predominant isoform expressed in MIN6B1 cells and islets compared to other forms of SDC. Immunofluorescence in mouse and human pancreas sections revealed that SDC4 is mainly expressed in β-cells compared to other pancreatic cells. Exposure of MIN6B1 and human islets to IL-1β dose-dependently induced a rapid and transient expression of SDC4 while SRC and STAT3 inhibitors decreased this effect. Exposure of human islets to Il-1β caused an increase of SDC4 shedding, however treatment with STAT3 and SRC inhibitors inhibited this effect. These results indicate that SDC4 is upregulated by IL-1β through the SRC-STAT3 pathway and this pathway is also involved in SDC4 shedding in islets.