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Diabetes increases in the worldwide by prevalence and numbers of complications related to it. The most common risk factor for foot ulcers in diabetic is peripheral neuropathy. In diabetic condition, Ca2+ concentration intracellular increases. NRF2 (Nuclear Factor Erythroid 2) acts as a bridging link in various inflammatory and apoptotic pathways impacting progress of diabetic neuropathy. The aim of this study is to predict the pathway of NRF2 activation that is mediated by the increased of intracellular Ca2+. Data interaction between Ca2+ and NRF2 were retrieved from STITCH (Search Tool for Interacting Chemicals) which were experimentally and prediction, then were analyzed computationally. Pathway analysis used Cytoscape software. The functional analysis was evaluated using STRING (Search Tool for the Retrieval of Interacting Genes/Proteins) database. The consequence of increased intracellular Ca2+ content is the increases of oxidative stress, ROS (Reactive Oxygen Species) and the translocation of the protein kinase Cα (PKRCA) to the plasma membrane as the initial step of their activations. This study reveals that activation NRF2 by Ca2+ intracellular which increases in diabetic condition through PRKCA, PRKCA phosphorylate NRF2 in its Neh2 domain at Ser-40. [ABSTRACT FROM AUTHOR]