The effect of tacrolimus (FK506) on peptic ulcer was evaluated using pyloric ligation (PL) model in rats. Tacrolimus was administered orally at different doses (1, 2 and 3 mg/kg) and it showed a gastric ulcer healing effect in a dose dependent manner. Gastric volume, total and free acidity and ulcerative index parameters were reduced in the tacrolimus treated rats as compared to pyloric ligated rats. The higher dose (3 mg/kg) treated group produced significant results similar to that of the ranitidine (50 mg/kg) treated group. Pretreatment with tacrolimus also produced significant (p<0.05) reduction in TBARS, total calcium, TNF-α, IL-8 and MPO whereas it showed an increase in GSH level at higher dose. The anti-secretory and anti-ulcerative effect of tacrolimus may be due to immunosuppressive actions by inhibition of calcineurin and the oxidative pathway. It can be concluded that tacrolimus can play an important role in the treatment of peptic ulcer disorder to improve the quality of life.