In order to explore the effects of retrograde infusion of chondroitin-sulfate via the pancreatic duct on cytoprotection and attenuation of oxidative damage during acute necrotic pancreatitis (ANP), male Wistar rats were randomly divided into three groups: A, B (experimental groups) and C (sham operation, control group). The rats in group A was subjected to retrograde injection of 5% sodium taurocholate via the pancreatic duct, and those in group B received chondroitin-sulfate therapy after ANP induction. All rats in three groups were killed at 6 h. The levels of malondialdehyde (MAD), total superoxide dismutase (SOD), glutathione (GSH), adenosine triphosphate (ATP) and serum amylase (SAM) were measured. The morphologic changes in pancreatic tissues were observed. It was found that the level of SAM was increased in group A and group B, with corresponding pathological changes of ANP. The levels of ATP, GSH and SOD in group A were decreased markedly and MDN increased significantly as compared with those in group B (P<0.01). In group B, the histopathologic damage was attenuated to a certain extent in comparison to that in group A. It was concluded that endogenous antioxidants were significantly reduced and lipid peroxidation increased during ANP. Retrograde infusion of chondroitin-sulfate via pancreatic duct could alleviate the pancreatic cell damage as a sort of scavengers of oxygen free radicals.