The renin-angiotensin system (RAS) plays important roles in various pathophysiological processes. However, the role of the RAS in pancreatic fibrosis has not been established. We investigated the role of angiotensin II (ATII)-angiotensin II type 1 (AT1) receptor pathway in the development of pancreatic fibrosis with AT1a receptor-deficient (AT1a^-/-) mice. To induce pancreatic fibrosis, AT1a^-/- and wild-type (WT) mice were submitted to three episodes of acute pancreatitis induced by six intraperitoneal injections of 50 µg/kg body weight cerulein at hourly intervals, per week for 4 consecutive weeks. Pancreatic fibrosis was assessed by histology and hydroxyproline content. Pancreatic stellate cells (PSCs) activation and the localization of AT1 receptors were assessed by Western bolt analysis for a-smooth muscle actin (-SMA) and immunostaining. Transforming growth factor-1 (TGF-1) mRNA expression in the pancreas was assessed by RT-PCR. Six intraperitoneal injections of cerulein induced acute pancreatitis in both AT1a^-/- and WT mice. There were no significant differences between two groups with regard to serum amylase and histological changes. Pancreatic fibrosis induced by repeated episodes of acute pancreatitis was significantly attenuated in AT1a^-/- mice compared with that in WT mice. This finding was accompanied by a reduction of activated PSCs. Dual-immunofluorescence staining in WT mice revealed that activated PSCs express AT1 receptors. The level of TGF-1 mRNA was lower in AT1a^-/- mice than in WT mice. Our results demonstrate that ATII-AT1 receptor pathway is not essential for the local pancreatic injury in acute pancreatitis but plays an important role in the development of pancreatic fibrosis through PSCs activation and proliferation.