Background: Exendin-4 (glucagon like peptide-1 agonist) is an insulinotropic gut peptide and is being evaluated for the regulation of blood glucose in diabetes mellitus. Objective: Evaluating the possible effects of exendin-4 administration with or without muscular exercise on diabetic male albino rats. Materials and Methods: Forty adult male albino rats were divided into four equal groups: Group I served as a normal control group, group II was diabetic control, group III was diabetic group treated with exendin-4, and group IV was diabetic group subjected to swimming exercise and receiving exendin-4. At the end of the experimental period, blood samples were collected for measuring of blood glucose, total cholesterol, triglycerides (TG), low density lipoproteins (LDL), high density lipoproteins (HDL) and C-peptide. Results: Alloxan-induced diabetes mellitus was associated with significant higher levels of serum blood glucose, total cholesterol, TG and LDL-C with significant lower levels of HDL-C and C-peptide as compared with the control normal group. Exendin-4 with or without muscular exercise showed significant lower levels of blood glucose, total cholesterol, TG and LDL-C levels, and significant higher levels of HDL-C and C-peptide as compared with the control diabetic rats. Conclusion: Exendin-4 therapy has a marked effect on improvement of blood glucose, C-peptide level and lipid profile. This was most probably due to increasing insulin sensitivity and decreasing hepatic fat biosynthesis. As regards the differences between the muscular exercise with exendine-4 group (group 4) and exendine-4 treated group (group 3), the obtained data showed a significant lower value of serum triglyceride in the muscular exercise with exendine-4 group compared with the exendine-4 treated group.