Eosinophilic pancreatitis (EP) is reported in human; however, the etiology and the role of eosinophils in EP pathogenesis is a poorly understood and not excusably explored. Therefore, it is interesting to examine the role of eosinophils in the initiation and progression of pancreatitis pathogenesis. Therefore, we performed real time PCR, ELISA, western blot, anti-MBP immunostaining, Chloroesterase and Massons' trichrome analysis were performed to examine transcript and protein levels of eosinophil active cytokines, chemokines, eosinophils, mast cells and collagen tissue accumulation. Pancreas is devoid of eosinophils in healthy individuals; however, eosinophils accumulation and degranulation in the tissue sections was observed in human pancreatitis. Herein, we first time located eosinophils accumulation and degranulation followed by induced mast cells and acinar cells atrophy in the pancreas of cerulein-induced murine model of pancreatitis. Additionally, induced transcript and protein levels of pro-inflammatory and pro-fibrotic cytokines, chemokines like IL-5, IL-18, eotaxin1 and eotaxin-2, TGF-β1, collagen-1, collagen-3, fibronectin and α-SMA were also observed in experimental pancreatitis in mice. Mechanistically, we report that eosinophil deficient GATA1 and endogenous IL-5 deficient mice were protected from the induction of proinflammatory and profibrotic cytokines, chemokines, tissue eosinophilia and mast cells, in cerulein-induced murine model of pancreatitis. These experimental data indicates that eosinophils accumulation and degranulation may be critical in promoting pancreatitis pathogenesis including fibrosis. Taken together, we report that eosinophil tissue accumulation has an important role in promoting pancreatitis pathogenesis including fibrosis that needs appropriate attention to understand and restrict disease progression and pathogenesis in human.