Background: Diabetes mellitus is one of the most common diseases in the world and number of patients with this disease increases every day. This disease with long time leads to harmful effects and has many complications as increase in blood pressure, disturbance in kidney functions and increase in blood lipids. It is, therefore, important to search for drugs which prevent harmful effects that result from diabetes mellitus. Objective: To study the effect of pioglitazone, fenofibrate and simvastatin treatment on diabetic albino rats. Materials and methods: A total number of 80 male albino rats weighing 150–200 g were obtained from Animal House, Assiut University (Assiut, Egypt) was used. They were housed at ordinary room temperature, exposed to natural daily light-dark cycles, fed with standard laboratory diet pellets and were given tap water. The standard diet was obtained from Animal Experimental Central. Results: Serum superoxide dismutase (SOD) increased significantly in diabetic rats treated with pioglitazone and diabetic rats treated with fenofibrate or simvastatin. Combination therapy of pioglitazone and simvastatin or fenofibrate have no synergistic effect on serum SOD. Serum glutathione (GSH) increased significantly in the diabetic rats treated with pioglitazone and the diabetic rats treated with fenofibrate or simvastatin. Combination therapy of pioglitazone and simvastatin or fenofibrate have no synergistic effect on serum GSH. Conclusion: The present study showed that treatment with fenofibrate or simvastatin did not increase body weight or lower blood glucose level of the diabetic albino rats significantly, but they improved significantly blood pressure, lipid profile, and serum level of antioxidants (GSH and SOD).