Chronic pancreatitis is a disease characterized by pancreatic fibrogenesis in response to sustained or repetitive injury. Pancreatic stellate cells (PSC) are interstitial cells that produce excessive extracellular matrix components during the process of fibrogenesis and therefore play a central role in the pathogenesis of chronic pancreatitis. Because the matricellular proteins thrombospondin-1 (TSP-1) and TSP-2 have a role in regulating fibrogenesis in other tissues, the expression of these major TSP isoforms in the whole pancreas was measured in a mouse model of repetitive pancreatic injury. Specifically, mice were treated with cerulein, 50 microg/kg/h x 6h with treatments repeated once or twice every 48 h. Expression was also evaluated in cultured PSC. PSC were isolated by outgrowth from normal mouse pancreas and expression of TSP-1 and TSP-2 was evaluated after serum-activation. The mRNA transcripts for TSP-1 and TSP-2 were increased, 16-fold and 87-fold respectively, in the pancreas in response to repetitive injury. In cultured PSC, these transcripts were also increased in response to serum and increases in mRNA were reflected by the secretion of TSP-1 and TSP-2 proteins by PSC into culture media. In summary, PSC may be an important source of both TSP-1 and TSP-2 in the pancreas in response to injury. These modulators of fibrogenesis could play a role in the development of pancreatic fibrosis that characterizes chronic pancreatitis.