Background/aims: To investigate the effects of different mechanisms on the development of pancreatitis after endoscopic retrograde cholangiopancreatography. Material and Methods: 40 male rats were randomly divided into four groups. After laparotomy, in Group 1, only duodenum was reached by a 24G cannula without performing any other procedure. In Groups 2, 3, and 4, biliopancreatic duct was cannulated transduodenally. Group 2 received no additional intervention after the cannulation. Group 3 received saline, whereas Group 4 received contrast agent into the duct. After a period of 24 hours, all rats were sacrificed. Laboratory tests for blood samples were performed and pancreatic tissue was also evaluated histopathologically. Results: Leukocyte, blood sugar, serum glutamic oxaloacetic transaminase, lactate dehydrogenase, amylase, C-reactive protein, and base excess parameters were evaluated. The values in Groups 2, 3, and 4 were found to be significantly higher than those in the control group, except for leukocyte count and base excess (p=0.551, p=0.031, p=0.0001, p=0.0001, p=0.0001, p=0.0001, p=0.683, respectively). Histopathological results demonstrated significant differences between the groups. Highest pathological damage scores were observed in Groups 3 and 4. Conclusion: Among different theories for the pathogenesis of post-endoscopic retrograde cholangiopancreatography pancreatitis, elevated intraductal hydrostatic pressure was observed to be the main underlying cause.