It has been proposed that cellular Ca2+ signals activate hormone secretion. In pancreatic β cells, which produce insulin, Ca2+ signals have been known to contribute to insulin secretion. In previous study, demonstrated that endocrine disrupting chemicals (EDCs) such as bisphenol A (BPA) and Octylphenol (OP) could causes increase in insulin level and insulin transcription factors. But in regulations of plasma glucose level were not decreased as much as insulin increase. For identifying this phenomenon, we evaluate the HOMA-IR which is used for calculating insulin resistance, trace that EDCs has ability to increase insulin resistance. We hypothesized that EDCs disrupts calcium homeostasis and the altered intracellular calcium levels may induce insulin resistance. The expression of genes involved in transporting calcium ions to the endoplasmic reticulum (ER) was decrease while the expression of those affecting the removal of calcium from the ER was increased. Depletion of calcium from the ER leads to ER-stress and can induce insulin resistance. Taken together, these results imply that the disruption of calcium homeostasis by EDCs induces ER-stress and leads to the insulin resistance. Additionally, findings from this study suggest that imbalances in calcium homeostasis due to EDCs such as BPA and OP could promote insulin resistance and its harmfulness especially to the Type I diabetes mellitus patients.