Objective: To observe the expression of S-phase kinase-associated protein 2 (Skp2) in the remnant liver tissue of rat with partial hepatectomy so as to determine its role in liver regeneration. Methods: Rats underwent 70% partial heptectomy and the their remnant liver tissues were collected at 12, 24, 48, 72 and 168 h after respectively pectively, after surgery. The expressions of Skp2 and proliferating cell nuclear antigen (PCNA) protein in the regenerating liver tissue were detected by immunohistochemical staining. Results: The expressions of Skp2 and PCNA in the remnant liver tissue of the rats with partial hepatectomy were all significantly higher than those of the sham operated rats at the observation time of 12, 24, 48 and 72 h, respectively after surgery (all P<0.01). Both the Skp2 and PCNA expression reached their maximal levels at 48 h after hepatectomy and there was a significant correlation between them (r=0.9085, P<0.05). Conclusion: Skp2 plays an important role in liver regeneration after partial hepatectomy.