Objective: To investigate the effects of vitamin E on collagen deposition induced by CsA administration in rats with caerulein pancreatitis. Summary Background Data: Cyclosporin A (CsA) transforms the fully-regenerative, self-limited form of caerulein pancreatitis into a chroniclike disease, in conjunction with increased TGF and myofibroblast proliferation. Vitamin E inhibits TGF release in mesangial cells and reduces CsA cytotoxicity. Methods: Wistar rats received CsA daily (20 mg/kg) and caerulein pancreatitis was induced on days 1 and 8 (Cr+CsA group). In a separate group, vitamin E (600 mg/kg/day) was administered starting 4 days before CsA. Three other groups received either vehicle, CsA, or caerulein alone. Thiobarbituric-reactive substances (TBARS), 8-isoprostanes, TGF and hyaluronic acid were measured in plasma obtained on the day the animals were sacrificed (day 15). Pancreases were weighed and processed for light microscopy to assess connective tissue and myofibroblast number. Pancreatic homogenates were also assayed for collagen (hydroxyproline) and TBARS content. Results: TBARS, 8-isoprostane, and TGF were elevated in CsA and Cr+CsA rats. Vitamin E treatment greatly decreased these parameters. Vitamin E also decreased the fall in pancreatic weight observed in Cr+CsA pancreas. Pancreatic hydroxyproline and plasma hyaluronic acid were increased in Cr+CsA rats, but were effectively reduced by vitamin E. Morphology showed improvement in fibrosis score and a decreased number of myofibroblasts in vitamin E-treated rats. Conclusion: Vitamin E reduces oxidative stress and collagen deposition during the development of experimental chronic pancreatitis. Adjuvant antioxidants may be of value in the treatment of chronic pancreatitis.