Chronic hyperglycemia may cause significant alterations in the status of some micronutrients (such as manganese cations) some of which can directly modulate glucose homeostasis.  In the meantime, it was reported that people with diabetes have low levels of manganese in the blood. This abnormality is also associated with exocrine pancreatic dysfunction evaluated by reduced concentrations of digestive enzymes. The purpose of this study is to investigate the interaction between endocrine and exocrine pancreatic functions, indicating the importance of manganese ions in pancreatic disorder. The present study composed of 40 rats that were divided into 4 groups; control (saline), control (MnCl₂), alloxan-induced diabetic and Mn²⁺-treated diabetic rats. Fasting blood glucose, manganese (Mn²⁺), calcium (Ca), lipase, a-amylase, malondialdehyde (MDA), glutathione reductase (GR), nitric oxide (N₂O₃) and superoxide dismutase (SOD) were measured in all groups. In this study, serum manganese, calcium, lipase, a-amylase, GR and SOD levels were decreased in diabetic groups compared to control groups. There was a clearly difference in serum pancreatic enzymes at P < 0.05 in Mn²⁺-treated diabetic group compared to untreated diabetic group. It can be concluded that exocrine pancreatic insufficiency (EPI) could be one of the mechanisms underlying (DM). Accordingly, it can be suggested that therapy of diabetes should address both endocrine and exocrine pancreatic functions.