Introduction: Chronic pancreatitis (CP) is a progressive fibro-inflammatory pancreatic disorder that eventually leads to damage of the gland. To date, appropriate therapy is still limited. This work investigated the effects of MSC-derived MVs and infliximab on CP induced by the repeated injection of L-arginine, and explored the possible underlying mechanisms. Materials and Methods: Forty adult male Wistar rats were randomized into control, arginine-treated, microvesicles-treated and infliximab-treated groups. Serum amylase, lipase and glucose levels were estimated. Rats were sacrificed and pancreatic sections from all groups were subjected to hematoxylin & eosin, Masson’s trichrome, Sirius red and immunohistochemical stains (insulin receptors and Bax). RNA was extracted for gene expression of TGF- β1, Pdx1, Fn-1, Collagen 1, mTOR, LC3- II, Beclin-1 and GAPDH. Results: Our results provided evidence for inflammation, fatty replacement and progressive fibrosis in arginine treated group. There was downregulation of insulin receptor expression and upregulation of Bax immune localization. Administration of infliximab and microvesicles ameliorated the arginine-induced effects with superior and more rapid effect regarding microvesicles. Conclusion: Microvesicles derived from mesenchymal stem cells provide a novel opportunity in comparison to infliximab as a promising theraputic for experimentally-induced chronic pancreatitis.