Salivary gland stem/progenitor cells belong to the endodermal lineage and may serve as good candidates to replace their dysfunctional counterparts. The objective of this study was to isolate large numbers of salivary gland tissue‐derived stem cells (SGSCs) from adult rats in order to develop a clinically applicable method that does not involve sorting or stem cell induction by duct ligation. We analysed SGSCs isolated from normal rat salivary glands to determine whether they retained the major characteristics of stem cells, self‐renewal and multipotency, especially with respect to the various endodermal cell types. SGSCs expressed high levels of integrin α6β1 and c‐kit, which are surface markers of SGSCs. In particular, the integrin α6β1⁺/c‐kit⁺ salivary gland cells maintained the morphology, proliferation activity and multipotency of stem cells for up to 92 passages in 12 months. Furthermore, we analysed the capacity of SGSCs to differentiate into endoderm lineage cell types, such as acinar‐like and insulin‐secreting cells. When cultured on growth factor reduced matrigel, the morphology of progenitor cells changed to acinar‐like structures and these cells expressed the acinar cell‐specific marker, α‐amylase, and tight junction markers. Moreover, reverse transcription–polymerase chain reaction (RT–PCR) data showed increased expression of pancreatic cell markers, including insulin, Pdx1, pan polypeptide and neurogenin‐3, when these cells formed pancreatic clusters in the presence of activin A, exendin‐4 and retinoic acid. These data demonstrate that adult salivary stem/progenitor cells may serve as a potential source for cell therapy in salivary gland hypofunction and diabetes. Copyright © 2012 John Wiley & Sons, Ltd.