Background: Aspartame is considered artificial sweetener accepted to replace sucrose. Pancreas has a vital role in carbohydrate metabolism. Aim: To study the effect of aspartame on the structure of pancreas. Materials and method: Eighteen 200-250gm albino Wistar rats obtained from the animal house, Faculty of Medicine, Zagazig University (ZSMRC). Rats were divided into three groups (6 animals for each group);control group: each rat will be kept without any treatment all over the experimental periods, aspartame treated group: was treated with aspartame at a dose of (250 mg/kg/day) once daily dissolved in water for six month and withdrawal group: was treated with aspartame at a dose of (250 mg/kg/day) once daily dissolved in water for six month then left without treatment for another month..Results: Rats' pancreas was injured by aspartame, as shown by histological changes such as deformed pancreatic acini with vacuolated cytoplasm and islets of Langerhans, increased collagen deposition around acini and blood vessels Additionally, the administration of aspartame resulted in elevated levels of serum amylase and lipase. When aspartame exposure was stopped, the rats' histological changes improved in comparison to when they were treated with aspartame. Conclusion: aspartame produces degenerative changes in the pancreas and causes enzymes level changes. Stoppage of aspartame exposure results in some restoration of the normal histological structure of the pancreas. So, it is recommended to stop the usage of aspartame.