© 2022. All Rights Reserved.Objective: Although different types of currents have been defined as store-operated Ca2+ entry (SOCE), the best characterized of these is Ca2+ release-activated Ca2+ currents (ICRAC). The SOCE pathway is an important way to generate cytosolic Ca2+ signals that regulate various biological processes. Abnormal SOCE appears to be one of the underlying causes of several diseases, particularly allergies, diabetes, inflammation, and cancer. In this study, the effects of hyperglycemia on SOCE activity were investigated by electrophysiological methods. Methods: In this study, rat basophilic leukemia-1 (RBL-1) cells were grown using DMEM solutions with high glucose (HG, 50mM) and normal glucose (5.5mM) concentrations. Following 72 h incubation period, SOCE activity was measured by Fura-2 based Ca2+ imaging technique and ICRAC currents recorded by voltage clamp method. Results: ICRAC current measurements were performed by the patch-clmap method and Fura-2 based Ca2+ imaging methods. For positive control experiments, using the PYR6 (SOCE blocker), it was confirmed that the currents were through the SOCE pathway. In addition, it was determined by two different methods that hyperglycemia significantly increased SOCE activity in RBL-1 cells compared to control values. Conclusion: Our findings reveal that the SOCE pathway may have an important role in the disturbances in Ca2+ homeostasis and Ca2+ content of ER/SR stores encountered in diabetic pathologies. Although these findings at the cellular level are limited, it is thought that they will make great contributions to future studies.