Activation of glial cells contributes neural disorders like depression and neuropathic pain through the release of nitric oxide and cytokines. The release depends on intracellular Ca2+ levels. One of the Ca2+ entry pathways is Ca2+ release-activated Ca2+ (CRAC) channel. Anti-depressants are used for treatment of trigeminal neuralgia, but the effects of anti-depressants on CRAC channel have remained unsolved. We therefore examined the inhibitory effects of anti-depressants on the CRAC channel using patch-clamp technique. We recorded the CRAC channel current in rat basophil leukemia (RBL) cells instead of glial cells. The reasons are 1) RBL cells are model cells to record the CRAC channel current, and 2) glial cells have many kinds of ion channels. The CRAC channel was activated by adding 10-mM IP3 in the pipette solution. Membrane potential was held at 0 mV and was changed every 3 s from -120 mV to 80 mV with the 50-ms ramp wave. The membrane current showed the inward rectification, and its polarity reversed at >50 mV. These properties are hallmarks of the CRAC channel. Duloxetine, one of the anti-depressants, inhibited the CRAC channel current at -100 mV in a time-dependent and a concentration-dependent manners. The rank order of the inhibition was duloxetine = paroxetine > nortriptyline > imipramine. Blockade of the CRAC channel might be one of the pain relief mechanisms of duloxetine.