Objective: Diabetes mellitus is a syndrome of multiple etiologies. Both type 1 and type 2 diabetes lead to multiple abnormalities of lipid and lipoprotein metabolism. The aim of this investigation was to study the influence of fenofibrate on the blood glucose lowering effect of glibenclamide. Materials and Methods: Glibenclamide (0.45, 0.23 mg/kg) and fenofibrate (18.1, 9.38 mg/kg) was treated to normal, diabetic rats, and normal rabbits. Blood samples were collected at various time intervals and were analyzed for blood glucose levels using a glucometer. Results: Co‑administration of fenofibrate with glibenclamide significantly elevated the blood glucose reduction exhibited by glibenclamide. Conclusion: The results obtained from single and multiple dose treatments clearly demonstrated the existence of drug‑drug interaction at the dose tested in animal models. Hence, this investigation would serve as a preclinical evidence for the effect of fenofibrate on the therapeutic efficacy of glibenclamide.