Propofol, most frequently used as general anesthetic, is thought to exert its anesthetic actions via GABA_Areceptors, however the precise mechanisms of its adverse actions remains unclear. We examined the propofol-induced elevation of intracellular calcium using SHSY-5Y neuroblastoma cells loaded by calcium indicator Fluo-4. Propofol at 0 – 200μM elevated the intracellular calcium in a dose-dependent manner. This phenomenon was not influenced by the elimination of extracellular calcium. And, the calcium elevation was abolished when intracellular or intra-endoplasmic reticulum (ER) calcium was depleted by BAPTA-AM or thapsigargin, respectively, suggesting that the calcium was mobilized from ER. Studies using various inhibitors including U-73122, Xestospongin C and dantrolene revealed that the propofol-induced calcium elevation was not mediated through G-protein coupled receptors, IP3 receptors or ryanodine receptors. We captured the live imaging of ER during the propofol stimulation using ER-tracker. Accompanying the calcium elevation, the ER structure was fragmented and aggregated, which was gradually restored. These phenomena might be involved in the exertion of various adverse effects of propofol including angialgia and propofol infusion syndrome.