CD45, a transmembrane protein tyrosine phosphatase required for signal transduction in leukocytes, has recently been found in pancreatic acinar cells. We have investigated the relationship between kinetic expression of CD45 on acinar cells during acute pancreatitis (AP) and the ability of these cells to produce tumour necrosis factor‐α (TNF‐α) through mechanisms sensitive to the cellular redox state. Flow cytometric analysis showed a significant decrease in the constitutive expression of CD45 in acinar cells from six hours onwards after inducing AP by bile‐pancreatic duct obstruction (BPDO) in parallel with a significant increase in acinar TNF‐α production. Changes in protein expression on the acinar cell surface preceded CD45 mRNA down‐regulation, which was not found until 12 hours after BPDO. N‐Acetylcysteine treatment delayed and reduced the down‐regulation of CD45 expression induced by AP and prevented acinar cells from producing TNF‐α. Our results show that CD45 expression is down‐regulated in acinar cells during acute pancreatitis by redox‐sensitive mechanisms, and they support the notion that CD45 negatively controls the production of cytokines in pancreatic acinar cells. Copyright © 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.