The hepatic response to systemic injury is characterized by alterations in the synthesis of plasma proteins, while acute injury to the liver can lead to rapid proliferation of hepatocytes. The hemopexin gene was found to be markedly induced in rat liver following both sham surgery (SS) and 70% partial hepatectomy (PH), models of systemic injury and hepatic proliferation, respectively. Transcriptional and post-transcriptional regulation of this gene was evaluated to examine the mechanisms of hemopexin mRNA expression in these models. Significant transcriptional activation was observed within 6 h of either surgery, with a more pronounced effect after PH. In both processes, transcription rates returned to baseline values by 24 h after surgery, although marked elevations in mRNA steady-state levels were noted for at least 72 h. At each time point, levels of hemopexin mRNA were more abundant following PH than after SS, in part due to greater transcriptional induction. In addition, posttranscriptional mechanisms appeared to contribute to the increased expression of hemopexin post-PH. The in vivo half-life of the 1.6-kb hemopexin transcript was determined to be considerably greater than 12 h in control, sham-operated, and PH animals. The exceptionally long mRNA half-life appears to be an important but complex factor in the kinetics of hemopexin gene regulation.