Inroduction: Cholestasis is a liver disease which means obstruction in bile duct. An increase in endogenous opioids have been reported after bile duct ligation (BDL) in rat. The aim of this study was to examine changes in gene expression of mu-opioid receptor 1 (MOR1) in hypothalamus and liver 21 days after BDL in rats. Methods: We used male Wistar rats weighing 300 ±20 g. After 21 days of BDL, body weight, liver weight and ratio of liver weight/body weight in different experimental groups of control, sham-operated and cholestatic were examined. The hypothalamus and the liver were then extracted in these groups. A semi-quantitive RT-PCR was also used for evaluating of MOR1 gene expression. Results: The results showed no significant difference in body weight between cholestatic and sham-operated groups. However, a weight decrease was observed in the cholestatic group. The results also showed a significant increase in liver weight and liver weight to body weight ratio in the cholestatic group. On the other hand, mRNA levels of MOR1 was significantly decreased in the hypothalamus and in the liver 21 days after BDL when compared to the sham-operated group. Conclusion: It can be concluded that gene expression of mu-opioid receptors has been affected by BDL in the hypothalamus and liver of cholestatic rats. This may suggest that changes in mu-opioid receptors may underlie changes in physiological functions such as body weight and feeding behavior in cholestatic rats.