Pancreaticobiliary duct (PBD) obstruction in rats is associated with hyperamylasemia, hyperlipasemia, pancreatic edema, inflammation, and subcellular enzyme redistribution in < 24 h. The purpose of our study was to investigate whether these changes are reversible. A catheter was placed in the distal PBD and tunneled subcutaneously to the nape of the neck where flow could be controlled. The distal end was secured into the duodenum. Animals were divided into five groups: Group I, free flow for 48 h; Group II, catheter obstruction for 24 h; Group III, obstruction for 48 h; Group IV, obstruction for 24 h followed by free flow for 24 h; Group V, obstruction for 24 h followed by free flow for 48 h. After killing, amylase and lipase were measured, pancreatic water content was determined, and morphologic damage was graded blindly for edema, inflammation, acinar dilatation, and cell injury. Both groups with temporary obstruction showed less morphologic damage than groups studied directly after obstruction. Pancreatic water content was lower after reversal than after a 48-h obstruction. Serum amylase and lipase peaked after 24-h obstruction and then dropped with either treatment. We conclude that continuous obstruction causes progressive pancreatic damage, whereas releasing the obstruction results in reversal of early structural and functional changes.