Orexin A (OXA) is a hypothalamic neuropeptide with both central and peripheral activities on insulin signaling and energy balance. Adiponectin is an adipocytokine which regulates metabolisms of lipid and glucose via its receptors AdipoR1 and AdipoR2. This study investigated immunohistochemical changes in expressions of OXA, its receptor OX1R in pancreas and AdipoR1 in skeletal muscle with a high fat diet (HFD)-induced insulin resistance (IR). Standard 45% fat and 60% fat diets were administered to Wistar rats for 3 and 8 w. OXA expression increased with both 3- and 8-w 45% fat diets. OX1R expression also increased with a 3-w 45% fat diet, but decreased with the 3-w 60% fat diet. OXA, OX1R, and AdipoR1 expressions decreased with a 8-w 60% fat diet. An early adaptation in context of OXA was observed in pancreas beta-cell to HFD-induced IR. OXA, OX1R, and AdipoR1 expressions decreased with either the higher amount or longer duration of HFD consumption.