Chitin, the most presence of biopolymer after cellulose, it consisting the major compound of crustacean shell. Chitosan is a biopolymer derived by deacetylation of chitin. Diabetes Mellitus (DM) is a collection of metabolic diseases characterized by chronic hyperglycemia resulting from defects in insulin secretion, insulin action, or both leading to metabolic abnormalities in carbohydrates, lipids, and proteins. Increasing the ROS level, damage the cell membrane lipid and proteins that change in cell metabolism thereby defect in function of tissue and organ. The aim of current study was to evaluate the effect of chitosan and nano-chitosan on guinea pigs with hyperglycemia. Diabetes induced by injection of dexamethasone for 5 weeks. Fasting plasma sugar significantly decrease in treatment groups (168.2±24.38 and 156.4±53.71). Also blood urea and creatinine levels significantly reduced in treatments groups.