Liver regeneration after partial hepatectomy is regulated by several factors that activate or inhibit hepatocyte proliferation. After hepatectomy, cytokines play an important role in injury to the remnant liver and subsequent impairment of liver regeneration. Tumor necrosis factor-a (TNF-a) and interleukin-6 (IL-6) are thought to be the initial cytokines associated with liver injury as well with regeneration. Pentoxifylline is a derivative of methyl xantine, inhibitor of TNF-a production, and has showed good benefits in sepsis, shock and acute pancreatitis. Aim: To evaluate if the blockade of the initial cytokine response by pentoxifylline could modulate the cytokine cascade, resulting in improved hepatocyte protection and proliferation. Methods: Thirty-two Wistar rats were submitted to partial hepatectomy (70%) and divided in 2 groups: Group P (n=16): rats received pentoxifylline (25mg/Kg intraperitoneally), and Group C (n=16): control rats that received saline solution intraperitoneally. Ten rats of each group were sacrificed after 2 hours for determination of serum levels of TNF-a, IL-6 and aminotransferases (AST, ALT). Liver tissues were obtained 48 hours after surgery and regenerative activity assessed by proliferating cell nuclear antigen (PCNA) expression and mitotic index. Results: Comparing the groups, two hours after surgery it was observed a significant decrease of serum TNF-a (8 ± 3 vs. 42 ± 15 pg/ml) and serum IL-6 (10 ± 5 vs. 59 ± 10 pg/ml) in the group treated with pentoxifylline (p<0.05). The levels of aminotransferase didn’t show difference between the groups. The PCNA labeling and mitotic index of the pentoxifylline group were significantly higher compared to the control group (p<0.05). Conclusion: The results suggest that pentoxifylline inhibits TNF-a production, ameliorates liver injury and accelerates hepatic regeneration after hepatectomy in rats.