Objective: To discuss the effect of dimethyl fumarate (DMF) on rats with L-arginine induced chronic pancreatitis (CP). Methods: Male Wistar rats were given DMF treatment (25 mg/kg) by oral lavage method; then Wistar rats were given the intraperitoneal injection of L-arginine for 5 times (250 mg/100kg, twice per time, each interval of 1 h) for building of CP model. Rats were divided into control group, CP group, DMF group and CP+DMF group. Rats in CP+DMF group were given the oral intragastric administration of DMF (25 mg/kg), while rats in control group and CP group were given the equal volume of normal saline. The weight of rats was evaluated and the intraperitoneal glucose tolerance test was performed (IPGTT, 2 g/kg). The islet of rats was isolated and then flow cytometry was employed to evaluate the quality and activity of islets. Meanwhile, the histology of non-endocrine tissues and levels of mycloperoxidase (MPO) and malondialdehyde (MDA) were detected. Results: Compared with control group. the weight of rats in CP group was significantly reduced at week 2, 4 and 6; the blood glucose significantly increased, AUC increased, the histopathological scores of pancreatic atrophy, acinar injury, edema and cellular infiltration increased, levels of MDA and MPO increased, the islet equivalent and islet activity decreased at 0. 30, 60, 120 and 180 min. Compared with CP group, the weight of rats in CP+DMF group significantly increased at week 2, 4 and 6; the blood glucose significantly decreased, AUC decreased, the histopathological scores of pancreatic atrophy, acinar injury, edema and cellular infiltration decreased, levels of MDA and MPO decreased, the islet equivalent and islet activity increased at 0, 30, 60, 120 and 180 min. Conclusions: DMF treatment can improve CP induced by L-arginine and islet function in rats.