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Background/Aim: Liver regeneration in small for sizes liver grafts and in subtotal hepatectomies may be suppressed increasing the mortality. TNF-α and IL-6 are strong promoters of hepatic regeneration after hepatectomy and recognized as initial phase cytokines in inflammatory response to systemic infection or injury, and in liver damage following hepatectomy or ischemia/ reperfusion injury. TGF-beta 1 is an anti-inflammatory cytokine and a potent growth inhibitor. There are evidences that TNF-α induces TGF-beta 1 expression in many cell types. We hypothesized that pentoxyfiline (PTX) an inhibitor of NF-kappa-B could improve liver regeneration by reducing TGF-beta 1 expression in the liver and the deleterious effects of high levels of TNF-α after partial hepatectomy. The aim of the present study was to evaluate the effect of pentoxifylline on liver regeneration after partial hepatectomy in rats.Methods: Wistar rats were randomized into 2 groups: Group C (n=26) animals submitted to 70% hepatectomy and saline administration, and Group PTX (n=26) animals submitted to 70% hepatectomy receiving pentoxifylline (25mg/kg). AST, ALT, TNF-α, and IL-6 serum levels were measured at 2 and 6 h after hepatectomy. At 48h after hepatectomy residual liver were removed and stained with hematoxylin-eosin. Hepatocyte proliferation was assessed by mitotic index and by proliferating cell nuclear antigen (PCNA) staining. Total RNA was isolated from liver tissues and qRT-PCR analysis for TGF-beta 1.Results: AST and ALT levels were not significantly reduced in rats treated by PTX. TNF-α and IL-6 blood levels increased at 2 and 6 hours after partial hepatectomy. Administration of PTX significantly decreased serum levels of TNF-α and IL-6 at 2 hours after resection. A significant reduction in TGF-beta 1 expression in liver tissue was observed in rats receiving PTX. The pathological results obtained 48 hours after the hepatectomy showed an increased mitotic index and PCNA labeling index in animals treated with PTX compared to saline treated rats Conclusion: Pentoxifylline decreases the systemic inflammatory response reduces liver TGF-beta 1 expression, enhancing liver regeneration and may be useful to improve the function of small for size liver grafts.