Background: Oxygen free radicals (OFR) have been implicated in the induction of acute pancreatitis (AP). Aims: The aim of this study was to determine the effect of ascorbic acid and N-acetylcysteine (NAC), potent antioxidants, against oxidative stress in AP. Methods: AP was induced by two i.p. injections of caerulein at 2-hour intervals ( 50 mu g/kg BW). One group received additionally an antioxidant mixture composed of L (+)- ascorbic acid (14.3 mg/kg BW) and NAC ( 181 mg/kg BW) i.p. The rats were sacrificed 12 h after the last injection. Oxidative stress markers were evaluated. Light-microscopic and ultrastructural examination was performed. Results: Formation of vacuoles, mitochondrial damage, and dilatation of rough endoplasmic reticulum, margination and clumping of chromatin were major ultrastructural alterations in AP group. Ascorbic acid + NAC prevented these changes. Small vacuoles were present within the cytoplasm of some of the acinar cells. Pancreas damage was accompanied by an increase in tissue malondialdehyde (MDA) levels ( p < 0.05), whereas a decrease was seen in catalase (CAT), superoxide dismutase ( SOD), glutathione peroxidase (GPx) activities and total glutathione (GSH) levels ( p < 0.005). Ascorbic acid + NAC decreased MDA levels but increased CAT, SOD, GPx activities and GSH levels ( p < 0.005). Conclusion: These results suggest that ascorbic acid + NAC is potentially capable of limiting pancreatic damage produced during AP via protecting. ne structure of acinar cells and tissue antioxidant enzyme activities. Copyright (C) 2006 S. Karger AG, Basel and IAP.