Background: A remarkable change in porcine islet morphology was observed after infusion of the pancreas with collagenase. The aim of the present study was to quantify these morphological changes and to assess whether these changes were due to the volume expansion caused by the collagenase entering the islet or the result of its digestive effects. Methods: This study was performed in pancreata of 28 crossbred pigs. First, eight pancreata were intraductally injected with collagenase by a continuous controlled pressure of 180 mmHg. Pancreas samples before collagenase infusion were used as controls. All tissue samples, both before and after infusion, were stained with anti-insulin. To quantify the morphological change of the islets, the mean beta cell/endocrine content ratio of the infused and not-infused tissue samples was compared. In a second experiment, 20 pancreata were similarly assessed after intraductal injection with Hank's balanced salt solution (HBSS). Results: In both the collagenase- and HBSS-infused groups, mean beta cell/endocrine content ratio was lower than in the control samples. The observed decline in the beta cell/endocrine content ratio was not significantly different between collagenase- and HBSS-infused pancreata. This suggests that the lower beta cell/endocrine content ratio and thus the morphological change in the infused tissue samples is caused by volume expansion of the fluid entering the islet and that the digestive effect of collagenase plays no or only a minor role. Conclusion: Morphological changes of islets are observed after infusion of pancreata with collagenase and HBSS, most likely caused by volume expansion due to fluid entering the islets.@en