ABSTRACT.Background. Results in pancreatic islet transplantation have improved during the last decade, but long term results remain disappointing. This is partly due to loss of islets in pre-transplant culture and immediate post-transplant period. Aim. Exendin is currently being used as drug therapy of type 2 diabetes mellitus. We wanted to investigate the in vitro effect of exendin on insulin secretion, pro- and anti-inflammatory cytokines in isolated pancreatic islets from rats.Materials and methods. Freshly isolated rat islets were obtained. One half of the cells was stimulated with exendin-4 (10nmol), the other served as controls. The incubation lasted for 48-72 hours. Subsequently the islets were stimulated with two different concentrations of glucose, respectively 1,67 mM and 20 mM, followed by measure of insulin secretion with EIA. Real time quantitative reverse transcription-polymerase chain reaction was used to assess the gene expression of IL-6, IL-10 and TNF-á. Cell free supernatant was harvested to quantify the protein secretion of IL-10 and TNF-á.Results. The insulin secretion was significantly better for the islets stimulated with exendin-4 for 48-72 hours as compared to controls (p=0,01, n=5). The gene expression of both pro- and anti-inflammatory cytokines were higher in the control group compared with the exendin group, but the protein secretion of IL-10 and TNF-á was higher in the exendin group.Conclusion. These findings suggest that exendin improve the insulin secretion, and may also reduce the inflammation in the islets. Islet culture with exendin before transplantation may therefore improve the outcome, but further investigations are needed.