The study was designed to evaluated exocrine pancreatic enzyme replacement therapy in hyperglycemic male rats induced by alloxan. A total of forty five adult male rats were use in this study, hyperglycemia was induce in thirty rats by single intraperitoneal (i.p) injection of Alloxan 100mg/kg/B.W. and the experimental (45) distributed into three groups: the first group (15 animals) administered distilled water orally service as control group. The second group hyperglycemic groups (15 animals) was treated with exocrine pancreatic enzyme(EPE).The third group hyperglycemic group non treated with exocrine pancreatic enzyme(NEPE). Blood samples were take in days 20,40,60 of experiment for measurement the following parameters: Serum some biochemical parameters, tissue pancreatic activity. The results showed that tissue orally gavages exocrine pancreatic enzyme(EPE) caused a significant elevation in tissue amylase activity in all treated group as compared to the control group. and significant increase in tissue amylase and decrease lipase and protease in concentration in EPE treated group as compared to the non-treated (NEPE) group. Also serum insulin concentration significant decrease and glucose showed a significant increase in EPE and NEPE groups when compared with the control group in after 20,40 and 60 day of experiment. The serum albumin showed significant decrease in all EPE groups when contrasted with the control group. And also The results illustrated that significant decrease in albumin concentration in all NEPE as compared to the control group. The Serum protein concentration was significant decrease in EPE and NEPE groups as compared to the control group in all experimental day. The results showed significant increase in serum cholesterol and triglyceride in EPE as compared to the NEPE . The results showed that PEP rats caused a significant decrease in serum high density lipoprotein (HDL)concentration as compared to the control group and significant decrease in HDL concentration in NEPE as compared to the control group. results showed that doses rats caused a significant(P