Inositol 1,4,5-trisphosphate receptors (InsP3Rs) modulate Ca2＋ release from intracellular Ca2＋ store and are extensively expressed in the membrane of endoplasmic/sarcoplasmic reticulum and Golgi. Although caffeine and 2-aminoethoxydiphenyl borate (2-APB) have been widely used to block InsP3Rs, the use of these is limited due to their multiple actions. In the present study, we examined and compared the ability of caffeine and 2-APB as a blocker of Ca2＋ release from intracellular Ca2＋ stores and Ca2＋ entry through store-operated Ca2＋ (SOC) channel in the mouse pancreatic acinar cell. Caffeine did not block the Ca2＋ entry, but significantly inhibited carbamylcholine (CCh)-induced Ca2＋ release. In contrast, 2-APB did not block CCh-induced Ca2＋ release, but remarkably blocked SOC-mediated Ca2＋ entry at lower concentrations. In permeabilized acinar cell, caffeine had an inhibitory effect on InsP3-induced Ca2＋ release, but 2-APB at lower concentration, which effectively blocked Ca2＋ entry, had no inhibitory action. At higher concentrations, 2-APB has multiple paradoxical effects including inhibition of InsP3-induced Ca2＋ release and direct stimulation of Ca2＋ release. Based on the results, we concluded that caffeine is useful as an inhibitor of InsP3R, and 2-APB at lower concentration is considered a blocker of Ca2＋ entry through SOC channels in the pancreatic acinar cell.