Pentoxifylline (PTX) has been shown to have beneficial effects on microcirculatory blood flow. In this study we evaluate the potential hemodynamic and metabolic benefits of PTX during hepatic ischemia. We also test the hypothesis that portal PTX infusion can minimize the I/R injury when compared to systemic infusion. Methods. Twenty-four dogs (18.1 ± 0.7 kg) were subjected to portal triad occlusion (PTO) for 45 min. The animals were assigned to 3 groups: CT (control, PTO, n = 8), PTX-syst (PTO + 25 mg/Kg of PTX IV, n = 8), and PTX-pv (PTO + 25 mg/Kg of PTX in the portal vein, n = 8). Animals were followed for 120 min. Systemic hemodynamics, gastrointestinal tract perfusion, oxygen-derived variables, and liver enzymes were evaluated throughout the experiment. Results. Animals treated with PTX presented significantly higher CO in the first hour after reperfusion, when compared to the CT (~3.7 vs. 2.1 L/min, P < 0.05). Alanine aminotransferase (ALT) was similar in the PTX groups two hours after reperfusion but significantly higher in the CT (227 vs. ~64 U/L, P < 0.05). Conclusion. PTX infusion was associated with hemodynamic benefits and was able to minimize liver injury during normothermic hepatic I/R. However, local PTX infusion was not associated with any significant advantage over systemic route.