Pharmacological doses of ceruletide administered intravenously to unconscious rats uniformly induces acute pancreatitis (AP) as well as a striking reduction in pure pancreatic juice (PPJ) and protein output. High-dose intravenous secretin administered to rats with ceruletide-induced AP effects a reestablishment of PPJ flow and a significant increase in PPJ protein output. Light microscopy of the pancreas in ceruletide-induced AP rats revealed marked acinar cell vacuolization and intense interstitial edema. By contrast, pancreatic histology in AP rats treated with high-dose secretin revealed a distinct lessening of acinar cell vacuolization and interstitial edema. We have established that high-dose intravenous secretin given to rats with ceruletide-induced AP is (1) not harmful, (2) reestablishes PPJ flow and evokes a partial restoration of protein output, and (3) appears to reduce pancreatic histopathology when compared to non-secretin-treated rats with AP.