Background: Diabetes mellitus is one of the most common endocrine disorders in all populations causing major health problem with long-term complications responsible for its mortality and morbidity. Oxidative stress has been suggested to be one of the factors in the development of diabetes and its chronic complications. Objective: Evaluation of the effects of glucagon like peptide-1(GLP-1) analogue (exendin-4) and antioxidants in diabetic male albino rats. Materials and methods: Forty adult male albino rats of local strain were chosen to be the model of the present study. They were left for two weeks in the laboratory room before any experimental interference for acclimatization with free access to water and rodent chow diet food. Induction of diabetes was done for all rats except the normal control group by a single subcutaneous injection of alloxan monohydrate 120 mg/kg with glucose by orogastric tube, then they were divided into four equal groups: group I (normal control group), group G II (diabetic control group),  group G III (treated by exendin-4 1nm/kg/day given by intraperitoneal injection for 4 weeks  and group G IV ( treated by exendin-4 as above combined with vitamin C 200 mg/kg/day and vitamin E14.4 IU/kg/day by gastric intubation for four weeks). Blood samples were withdrawn for determination of blood glucose and lipid profile. Results: Treatment of diabetic rats by exendin-4 and antioxidants (vitamin C and E) caused significant reduction of blood glucose, total cholesterol, LDL and TG, and significant elevation of HDL levels in comparison to diabetic control group. Conclusion: Exendin-4 therapy as well as antioxidant, has a marked improvement of blood glucose level and lipid profile in male albino rats