Cholestasis caused by the excessive accumulation of bile within the liver, due to intrinsic or extrinsic factors. Cholestasis side effects are associated directly or indirectly with the reduction of bile flow and the confinement of materials related to bile secretion (such as bile acids, bilirubin, and cholesterol). On the other hand, some factors such as opioids, alkaline phosphatase, endotoxin and nitric oxide increase in blood, which could cause tissue damage. Since water intake reduces during cholestasis and hypothalamic nuclei such as paraventricular and supraoptic nucleuses are involved in the regulation of body water; Therefore, in this study, the histopathological changes of hypothalamic nuclei were evaluated. Male Wistar rats weighing 200–250 g were randomly divided into three groups. Three sets of seven groups were unoperated control, sham-operated and bile duct-ligated rats. The tissue samples were analyzed using histotechnique and light microscope. Brain tissue necrosis in paraventricular and supraoptic nucleus in cholestatic rats increased, but in the sham and control rats no changes were observed and also cholestasis caused wrinkle chromatic nuclei and increased thickness of hypothalamic nuclei. Because endotoxin causes tissue trauma, it is likely increased endotoxin may leads to tissue changes in the brain.