Glucagon like peptide-1 is a glucoincretin hormone that can act through its receptor (GLP-1R) on pancreatic β cells and increase insulin secretion and production. GLP-1R agonists are being used clinically to treat type 2 diabetes. GLP-1 may also regulate the exocrine pancreas at multiple levels including inhibition through the CNS, stimulation indirectly through insulin and stimulation directly on the acinar cells. However, it has been unclear whether GLP-1R is present in pancreatic acini and what physiological functions these receptors regulate. In the current study, we utilized the GLP-1R knockout mice to study the role of GLP-1R in acinar cells. RNA expression of GLP-1R was detected in acutely isolated pancreatic acini. Acinar cell morphology and expression of digestive enzymes were not affected by loss of GLP-1R. GLP-1 induced amylase secretion in WT acini. In GLP-1R knockout (KO) mice, this effect was abolished, whereas VIP induced amylase release in KO acini showed a similar pattern to that in WT acini. GLP-1 stimulated cyclic AMP production and increased PKA-mediated protein phosphorylation in WT acini, and these effects were absent in KO acini. These data show that GLP-1R is present in pancreatic acinar cells and that GLP-1 can regulate secretion through its receptor and cAMP signaling pathway.