Abstract There is increasing evidence implicating oxidative stress in the pathogenesis of both acute and chronic pancreatitis. Because ethanol is a major cause of pancreatitis in Western society, the aim of this study was to determine whether chronic ethanol administration results in oxidative stress in the pancreas. Twelve pairs of rats were fed a diet containing ethanol as 36% of calories or an isocaloric control diet for 4 weeks. Ethanol feeding resulted in a 46% increase in pancreatic malondialdehyde ( p = 0.006). In addition, total pancreatic glutathione was increased by 22% ( p = 0.005). These biochemical changes occurred in the absence of histologic evidence of inflammation or necrosis, implying that the observed oxidative stress is a primary phenomenon rather than part of an inflammatory response.