Orexin-A has been suggested to control hypertension, feeding behavior, and obesity. We recently established that long-term consumption of thiamine water by obese diabetic rats leads to reduced obesity and metabolic disorders. In addition, we found that drinking thiamine water daily may modulate oxidative stress-related diseases, such as diabetes and its complications. In the present study, we focused on obesity-related hypertension and plasma orexin-A levels in Otsuka Long–Evans Tokushima Fatty (OLETF) rats under oxidative stress conditions and assessed their cerebral ADP-ribosylated protein expression after drinking thiamine water. The thiamine water-drinking group was administered 2 g thiamine/L in drinking water. Plasma orexin-A content was measured by ELISA testing. ADP-ribosylated protein expression was analyzed in the brain of OLETF rats using Western blotting. Primary experimental characteristics, body weight, and caudal blood pressure were similar among the groups. However, at 28 weeks of thiamine water-drinking, significant decreases in body weight and systolic blood pressure were observed in the diabetic-thiamine group compared to those in the diabetic-control group. Moreover, obese diabetic rats exhibited increased plasma orexin-A levels and poly-ADP-ribosylated protein levels in the brain. Notably, the enhanced plasma orexin-A level and cerebral oxidative stress conditions of the obese diabetic rats were attenuated by drinking thiamine water. The relationship between consumption of thiamine in drinking water and obesity-related hypertension and cerebral oxidative stress status via modulation of plasma orexin-A levels requires further investigation. It is noteworthy that the upregulation of orexin signaling may not only cause hypertension, but also maintain obesity in polyphagia-induced OLETF rats.