Although studies show protective effects of 17-estradiol (E₂) or prolactin (PRL) treatment in male rats following trauma-hemorrhage (T-H), the mechanism of the salutary effects of these agents remain unknown. Since E₂ modulates PRL receptor (PRL-R) expression in the liver, we examined whether E₂ treatment following T-H has any effects on hepatic PLR-R gene expression. Male Sprague-Dawley rats were subjected to trauma (i.e., 5cm midline laparotomy) and hemorrhage (35-40 mmHg for 90 min followed by fluid resuscitation (Ringers lactate)) or sham operation and the treated with E₂ (50µg/kg BW, subcutaneously) or vehicle immediately before resuscitation. Liver samples were collected at 3 h thereafter and PRL-R mRNA expression determined by PCR. Liver expression of PRL-R short form gene was unaffected by T-H, whereas that of long form gene was suppressed. Treatment of T-H rats with E₂ significantly increased PRL-R short form gene expression and normalized PRL-R long form gene expression to sham levels. In the isolated hepatocytes, PRL-R short form gene expression was predominant as compared to the long form gene. In contrast, only short form was detected in Kupffer cells. In vitro treatment by E₂ demonstrated an increase in the PRL-R long form gene in hepatocytes, but E₂ had no effect on PRL-R short form gene expression in either the Kupffer cells or hepatocytes. Thus, E₂ treatment following T-H in males appears to directly upregulate PRL-R long form gene expression in hepatocytes. However, the upregulation of PRL-R short form might involve the interaction of multiple cell type in the liver.