Nanoparticles drug delivery systems are nanometric carriers that enhance drugs delivery and therapeutic action. The current study aimed to investigate the effect of daily oral administration of metformin and metformin nanoparticles (45 mg/kg b. w.) for 28 days on rats subjected to type 2 diabetes.24 male albino rats were divided into 4 groups, group 1 normal control, group 2 diabetic control, group 3 diabetic rats treated with metformin drug, group 4 diabetic rats treated with metformin chitosan nanoparticles drug with dose (45 mg/kg b. w.) for 28 days. Compared to diabetic control, a significant increase in body weight and decreased organs weights (liver, heart, kidneys) were recorded in diabetic rats treated. With metformin. Also, data was recorded in a significant decrease in serum glucose levels of treated diabetic rats compared to diabetic control rats. Increased serum levels of liver function (ALT, AST, ALP) and kidney function (Urea, Creatinine, Uric acid) parameters were detected in diabetic rats. Treatment with metformin and metformin nanoparticles caused a significant decrease in AST and ALT activity along with a significant decrease in creatinine and urea levels, the effects that were reversed upon metformin administration with the nanoparticles. However, the metformin nanoparticles have shown a superior effect. Various histopathological alterations were detected in the pancreas, liver, and kidney of diabetic animals. Alleviation of the histopathological changes was achieved following metformin with the nano-metformin affording better protection. In conclusion, The effect of metformin nanoparticles appears better than metformin in alloxan-induced diabetes in rats.