Nuclear factor erythroid 2-related factor (Nrf2) is a master regulator of redox homeostasis. Downstream targets of this transcription factor provide protection against oxidative damage to normal and cancer cells, and thus impact these cells in a multifaceted way. On the one hand, Nrf2 decreases the level of reactive oxygen species and prevents carcinogenic tissue transformation. On the other hand, Nrf2 mediates cellular detoxification of electrophiles and thus supports cancer progression by increasing resistance to therapy.  Pancreatic acinar cells (PACs), which produce and store digestive enzymes, are the main cellular components of the exocrine pancreas. Enzyme secretion is tightly controlled in these cells by intracellular calcium signals. Dysregulation of these signals may lead to premature enzyme activation, auto-digestion of the organ and sterile inflammation of the pancreas (pancreatitis) – a risk factor for pancreatic cancer development. In the present study we aimed to investigate whether the lack of transcriptional activity of the Nrf2 protein affects calcium signals in pancreatic acinar cells. In order to address this question, we have compared calcium signals recorded in real time in PACs isolated from 8-week-old male wild type (WT; N = 3) or Nrf2 transcriptional knock-out mice (tKO; N = 3). Calcium responses were evoked by acetylcholine as a physiological stimulus, or pathophysiological agents, such as menadione which is an inducer of oxidative stress and bile acid salts, potent triggers of acute pancreatitis. Data were analysed using a Mann-Whitney U test and the significance threshold was set at p = 0.05. Our results revealed that PACs isolated from the Nrf2 knock-out animals were characterized by a decreased calcium response to physiological stimuli. However, calcium signals in response to pathological cues were increased compared to the wild-type counterparts. This may point towards a lower capacity of the Nrf2 tKO pancreatic cells in dealing with oxidative stress.