Background: Chronic pancreatitis (CP) is a disease characterized by permenant damage of the pancreas. Objective: evaluate the possible therapeutic effect of ghrelin and exosomes derived from mesenchymal stem cells in the treatment of chronic pancreatitis. Materials and Methods: Sixty-two adult male albino rats were randomly divided into six groups. Group I (control group). Group II (affected group): Rats were injected intraperitoneally by l-arginine at a dose of 500 mg/100g body weight that is 2.5 ml of l-arginine solution/100g body weight five times at three days intervals, dissolved in citrate buffer. Group III (recovery group). Group IV: CP treated with ghrelin. Group V: CP treated with MSCs derived exosomes. Group VI: CP treated with ghrelin and MSCs derived exosomes. Pancreatic specimens were taken and prepared for histological and immunohistochemical examination. Results: Group II and III showed signs of degeneration. There were distorted acini with cytoplasmic vacuolation, decrease number of cells of islets, empty spaces between islets, dilated congested blood vessels and cellular infiltration. Furthermore, there was intense positive collagen fibers deposition, iNOS and CD8 immunostaining. Groups IV and V showed improvement of some histological microscopic changes in group II, significant decrease (P