Diabetes mellitus and brain toxicity are closely linked, and oxidative stress, obesity, insulin resistance, and glucose toxicity can affect the brain. Orexin-A, also known as hypocretin-1, through its activated receptor, participates in many physiological processes. Orexin-A has been associated with feeding behavior, obesity, and pathogenesis of Alzheimer's disease. We have recently established that high-dose thiamine in obese diabetic Otsuka Long–Evans Tokushima Fatty (OLETF) rats leads to reduced obesity and metabolic disorders. Additionally, we found that plasma orexin-A levels in OLETF rats can be modulated by thiamine supplementation under conditions of oxidative stress. Here, we focused on orexin-A in obese diabetic OLETF rats, which at 58 weeks of age and as expected, showed an increase in body weight and blood glucose levels. Plasma orexin-A was measured by ELISA and tended to be higher in obese diabetic OLETF rats than in non-obese diabetic control rats. We evaluated hypocretin receptor 1 (Hcrtr1, also orexin-A receptor) gene expression in the brain of diabetic OLETF rats by reverse transcription (RT)- polymerase chain reaction (PCR) and show that, compared to controls, diabetic OLETF rats exhibited greater orexin-A receptor gene expression in the brain. The results presented here are expected to provide a better understanding of the role of orexin-A and its contribution to brain toxicity in obese diabetic rats.