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Abstract  The key pathological features of chronic pancreatitis are chronic inflammation, acinar atrophy, and pancreatic fibrosis. We have previously shown that ellagic acid, a plant-derived polyphenol found in fruits and nuts, inhibited activation of pancreatic stellate cells, a major profibrogenic cell type in the pancreas, in vitro. Here we examined whether ellagic acid inhibited the development of pancreatic fibrosis in vivo. Ellagic acid was administered orally in the diet to ten-week-old male Wistar Bonn/Kobori rats, an experimental model of spontaneous chronic pancreatitis, for ten weeks. Ellagic acid (100 mg/kg body weight/day) attenuated pancreatic inflammation and fibrosis. The protective effects were confirmed by an increase in pancreatic weight and decreases in myeloperoxidase activity (an index of neutrophil infiltration), collagen content, transforming growth factor-β1 expression, and the number of α-smooth muscle actin-positive cells (activated pancreatic stellate cells) and ED-1-positive cells (macrophages/monocytes). Ellagic acid inhibited the production of reactive oxygen species in pancreatic stellate cells in response to transforming growth factor-β1 or platelet-derived growth factor. Our results suggest that ellagic acid might be a candidate for treatment of chronic pancreatitis. [ABSTRACT FROM AUTHOR]