Opuntia ficus-indica has traditionally been used in prevention and treatment of various diseases such as diabetes mellitus. The current study was performed to determine whether Opuntia ficus-indica is associated with diabetes. Diabetic rat models were induced with streptozotocin (STZ). This study divided rats into 1 day (short-term) and 4 consecutive weeks (long-terms) of daily administration. These groups were subdivided into four groups each other for assessment of blood glucose level as follows: Group 1, untreated rats given distilled water; Group 2, untreated rats given Opuntia ficus-indica; Group 3, STZ-induced diabetic rats given distilled water; Group 4, STZ-induced diabetic rats given Opuntia ficus-indica. Blood glucose level was measured for one day and four weeks. In addition, serum markers of alanine aminotransferase (ALT), aspartate transaminase (AST), cholesterol, and creatinine were determined, and total protein triglycerides were measured at four weeks. Blood glucose level was highest in both groups (Group 3 and Group 4) at 30 minutes and two weeks and gradually decreased in a time-dependent manner. The difference in blood glucose among the four groups was significant (p < 0.05). Additionally, the levels of ALT, AST and triglycerides were significantly decreased by Opuntia ficus-indica.