Objective - to study structural and histochemical changes in neurons of the rat frontal cortex after ligation of common bile duct. Materials and methods. Frontal cerebral cortex was examined in 72 male outbred albino rats of 200±25 g body mass. Histological and histochemical methods were used to study the microstructural changes of the pyramidal neurons in all the layers of frontal cortex 2, 5, 10, 20, 45 and 90 days after common bile duct ligation and cholestasis development (experimental group) or after a sham operation (control group). Results. It was found that common bile duct ligation in rats followed by cholestasis resulted in a profound histological and histochemical alterations in the neurons of frontal cerebral cortex that included the changes of cell size and form, emergence of the hyperchromic wrinkled neurons and ghost neurons. Disturbance of energy and plastic metabolism of neurons lead to the death of the experimental animals. Consequences of a cholestasis appeared in rat brain at days 2-5 and reached their maximum at days 10-20. At protracted time periods after the operation (days 45-90) in the group of surviving animals these disturbances gradually regressed though consequences of a cholestasis were manifested by the foci of neuronal loss in all the layers of frontal cortex. Conclusions. It is assumed that survival of rats after ligation of the common bile duct is due to the formation of the biliary tract bypasses resulting in the disappearance of cholestasis, and to high adaptive capabilities of neurons.