Chronic pancreatitis is a progressive disease characterized by irreversible morphological changes to the pancreas, typically causing pain and permanent loss of function. It is a poorly understood disease with the pathogenesis remaining unclear. The authors' previous data demonstrated that the inhibition of Toll‑like receptor 4 (TLR4) using TLR4 antagonist kinase (TAK)‑242 attenuates taurocholate‑induced oxidative stress via the regulation of mitochondrial function in the pancreatic acinar cells of mice. In the present study, the effect of TAK‑242 on trinitrobenzene sulfonic acid (TNBS)‑induced chronic pancreatitis was investigated in rats. The results revealed that TAK‑242 attenuated the severity of chronic pancreatic injury, and regulated extracellular matrix secretion and cellular immunity. In addition, TAK‑242 treatment significantly decreased cell apoptosis, as evidenced by the reduction in Terminal deoxynucleotidyl transferase dUTP nick end labeling‑positive cells in pancreas tissue sections, and also promoted cell proliferation in TNBS‑treated animals. Furthermore, the results of the calibrated von Frey filament assay demonstrated that TAK‑242 could prevent the pancreatitis‑induced referred abdominal hypersensitivity. In summary, TAK‑242 exhibits protective effects against TNBS‑induced chronic pancreatitis and may be a potential therapeutic strategy for the treatment of patients with chronic pancreatitis.