Significance: The renin–angiotensin system (RAS) is a circulating hormonal system involved in the regulation of blood pressure and circulating fluid electrolytes. Recent findings have revealed that locally generated angiotensin (Ang) II plays a pivotal role in normal physiology as well as pathophysiology in various tissues and organs, including the pancreas. This review article summarizes current progress that has been made in elucidating the putative roles of Ang II in both acute and chronic pancreatitis. Recent Advances: A convergence of evidence suggests that the underlying mechanism may involve reactive oxygen species (ROS)-generating systems, such as nicotinamide adenine dinucleotide phosphate oxidase, and subsequent elevation of proinflammatory and profibrogenic gene expression as well as protein activity. More importantly, Ang II-induced ROS interacts with other ROS-generating systems to positively feed-forward the ROS-induced signaling. Critical Issues and Future Directions: Advances in basic research indicate that RAS blockers may provide potential therapeutic role for the management of pancreatic inflammation and, more importantly, pancreatitis-associated complications. Genetic alterations resulting from a malfunction in the epigenetic control of pancreatic RAS could be a causative factor in the development of pancreatitis. Antioxid. Redox Signal. 15, 2743–2755.
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