Background: Glycemic control is important in diabetes mellitus to minimize the progression of the disease and the risk of potentially devastating complications. Inhibition of the sodium glucose cotransporter (SGLT2-inhibitor) induces glucosuria and has been established as a new anti-hyperglycemic strategy. Canagliflozin is approved as sodium glucose co-transporter 2 inhibitors (SGLT2-inhibitor), plays a distinct and complementing role in glucose homeostasis. Objective: Comparing the effects of Canagliflozin on streptozotocin-induced type-I and type- II- diabetes in adult male albino rat. Materials and Methods: Sixty male albino rats were randomly categorized into 6 equal groups; Group I (Normal control group): Rats received 2 ml/100 g Na citrate buffer by intraperitoneal injection, Group II (Normal-Canagliflozin-treated-group): Rats received Canagliflozin (10 mg/kg/day, orally), Group III (Streptozotocin-induced type-I diabetic group): Rats were subjected to induction of diabetes by a high single intraperitoneal injection of streptozotocin 65 mg/kg body weight in citrate buffer,  Group IV (Streptozotocin- nicotinamide- induced type-II diabetic group): The overnight fasted rats were subjected to induction of diabetes by a small single intraperitoneal injection of streptozotocin 40 mg/kg body weight (2 ml/100 gram) in citrate buffer and nicotinamide in a dose of 110 mg/kg boy weight 15 minutes before streptozotocin injection, Group V (Streptozotocin + Canagliflozin): Received a high dose of streptozotocin (65 mg/kg body weight) and Canagliflozin (10 mg/kg/day, orally), and Group VI (Streptozotocin + nicotinamide + Canagliflozin): Received a small dose of streptozotocin (40 mg/kg body weight), nicotinamide (110 mg/kg body weight),   and Canagliflozin (10 mg/kg/day, orally).  At the end of the experimental period, blood samples were collected for measuring of fasting serum glucose level, insulin level, C-peptide level, total cholesterol, triglycerides (TG), cholesterol- low density lipoproteins (LDL-C), cholesterol-high density lipoproteins (HDL-C), aspartate transaminase (AST), and alanine transaminase (ALT). Histopathological studies of the pancreas were done. Results: Streptozotocin-induced diabetes mellitus was associated with significant higher levels of serum blood glucose, total cholesterol, TG and cholesterol- LDL-C, AST, and ALT, with significant lower levels of insulin, C-peptide, and HDL-C as compared to the control normal group.  Canagliflozin showed significant lower levels of blood glucose, total cholesterol, TG, LDL-C, AST, and ALT, and significant higher levels of insulin, C-peptide, and HDL-C as compared with the diabetic rats. There were insignificant changes also between groups V and VI in all parameters. Conclusion: Canagliflozin improved glycemic, lipidemic disturbances, liver enzymes, and have a potent tissue protective and regenerative effects for the pancreas.