Objective BNIP3 mediate mitochondrial dynamic equilibrium in liver fat metabolism and glucose metabolism. Mitochondrial metabolism plays an important role in liver regeneration. Some studies have shown that EPO may promote liver regeneration, but the exact mechanism is remained to be elucidate. To study the effect of recombinant human erythropoietin (rhEPO) on liver function and liver regeneration after partial hepatectomy in rats, as well as the expression of BNIP3 and TNF-αmRNA in regenerating liver tissue. Methods 36 Wistar rats were randomly divided into the rhEPO group and blank group, and were submitted to 70% hepatectomy. The rhEPO group received 3000IU/kg of rhEPO throught portal vein injection and the blank control group received normal saline. Parameters of liver function and liver regeneration were assessed 1，3，5 days after 70% hepatectomy by means of automatic biochemical analyzer，immunohistochemical staining，ELISA assay and real-time PCR. Results 1 day after hepatectomy alanine aminotransferase (ALT) were significantly lower in rhEPO group than the blank group (P <0.05). 1,5 day after hepatectomy Ki-67 labeling rate in rhEPO group were significantly higher than the blank group (P <0.05). 1day after liver resection serum TNF-α in rhEPO group were significantly higher than the blank group (P <0.05), 1,3d ays after hepatectomy serum IL-6 in rhEPO group were significantly higher than the blank group(P <0.05). 1,3days after liver resection, BNIP3 and TNF-α mRNA in rhEPO group were significantly higher than the blank group (P <0.05). Conclusions Portal vein injection of rhEPO can protect liver function and promote liver regeneration, the mechanism may be related to BNIP3 and TNF-α.