BACKGROUND: Acute pancreatitis (AP) is inflammation of pancreas in which pancreas enzymatic activity is increased. Parasym- pathetic innervation of pancreas plays an important role in several functions of pancreas. Botulinum toxin (BTx) might be a tool to suppress the pancreas activity in AP. METHODS: In the preliminary experimental study, BTx (15U/kg) was administered directly and intraductal ways. After 10 days, blood amylase, lipase, trypsinogen, insulin, and glucagon levels were compared and no significant difference was seen between groups. Intraductal BTx administration is preferred for experimental AP model in rats; control, AP, intraductal BTx, and AP with Intraductal BTx (AP+BTx). AP was created by intraperitoneal injection of cerulean 20 μg/kg/injection (5 times). After 24 h, serum amylase, lipase, IL-6, IL-1β, TNF-α, and IL-10 were measured and pancreas tissue was evaluated for inflammation and necrosis. RESULTS: Mean serum amylase, lipase IL-6, IL-1β, and TNF-α levels of the AP group were significantly higher compared to the other groups (p<0.05). However, there was no significant difference between the amylase and lipase levels of control, BTx, and AP+BTx groups. Serum insulin and glucagon levels in AP group were significantly higher than control and BTx groups (p<0.05). However, there is no significant difference between the insulin and glucagon levels of AP and AP+BTx groups. in pathological evaluation. In AP+ BTx group, there is less amount of centrilobular necrosis and there is mild inflammation and hyperplasia of pancreatic duct epithelium. CONCLUSION: Administration of intraductal BTx suppressed the AP without making significant suppression in endogenous activity of pancreas.