The activation of transcription factor nuclear factor kappa B (NF-kappa B) occurs early in acute pancreatitis (AP) simultaneously with intracellular trypsinogen activation. Double-stranded RNA-dependent kinase (PKR) promotes the activation of NF-kappa B and the production of pro-inflammatory factors including tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6). The rat and rat pancreatic AR42J cells were treated by cerulein to establish AP models, showing PKR increased. TNF-alpha, IL-6 and lactate dehydrogenase (LDH) in AP pancreatic tissues and cerulein-treated AR42J cells increased, while PKR knockdown in AR42J cells reversed cerulein-induced inflammatory response and pancreatic cell injury. In addition, inhibitor of kappa B kinase a (IK kappa a), phosphorylated P65 (p-P65), P65 increased in cerulein-treated AR42J cells. Meanwhile, in cerulein-treated AR42J cells, interaction between PKR and IKKa, as well as the co localization and nuclear accumulation of PKR and P65, were detected. Furthermore, cerulein induced the phosphorylation and nuclear translocation of P65, which indicated the activation of NF-kappa B, while PKR knockdown hindered NF-kappa B activation to alleviate pancreatic cell injury. In summary, PKR might promote NF-kappa B activation via facilitating its phosphorylation and nuclear translocation, thus accelerated inflammatory response and pancreatic cell injury in AP, implying a novel molecular target for the treatment of AP. (C) 2018 Published by Elsevier Inc.