Inhibitors of DNA binding proteins (Ids) are implicated in the control of proliferation and differentiation. Herein, we tested the hypothesis that Id2 could stimulate proliferation and survival in differentiated pancreatic beta cells. We showed that Id2-enhanced proliferation of a growth-arrested pancreatic beta cell line (BTC-tet). This was mediated by the Rb pathway, as shown by an E2F1-driven reporter assay and Western immunoblot of phosphorylated Rb protein. Id2 also induced expression of Bcl-2, accompanied by a significant reduction of critical mediators of cytokine stimulation, including p38 MAPK and NFκB, as well as apoptosis markers, caspase-3 and Annexin-V. Overall, our data suggest that Id2 enhances proliferation and survival of growth-arrested BTC-tet cells.