Ischemia reperfusion injury (IRI) is an increasingly important problem in clinical transplantation. Its pathogenesis involves a variety of mechanisms including the increase of proinflammatory mediators. Different prophylactic and therapeutic measures have been investigated to prevent lung injury secondary to IRI. Lidocaine (Lido) is a commonly used local anesthetic agent which has also been found to possess anti-inflammatory activity in several disorders but data available are not enough to demonstrate this fact on lung tissue. This study was designed to investigate a possible protective effect of lidocaine on lung injury secondary to IRI. Two groups (LIDO and control) of six large-white pigs each were submitted to a left lung auto-transplant. Both groups received the same anesthetic induction (fentanyl 3 ug/Kg, propofol 3 mg/Kg, atracurium 0,5 mg/Kg). In addition animals of LIDO group received a continuous IV of lidocaine 1,5 mg/kg during surgery. Lung tissue samples were taken in four different moments: 1) pre-pneumonectomy (5 min before pulmonary artery clamp), 2) pre-reperfusion (5 min before reperfusion), 3) 30 min post-reperfusion (PR30) and 4) 60 min post-reperfusion (PR60). mRNA and protein expression of different proinflammatory mediators (interleukin 1 (IL-1), tumor necrosis factor alpha (TNFa), monocyte chemoattractant protein 1 (MCP-1), interleukin 10 (IL10), and endothelial nitric oxide synthase (eNOS)) were measured. Each lung sample was immediately frozen in liquid nitrogen. mRNA expression was measured by means of RT-PCR using the SYBR Green PCR Master Mix and 300 nM concentrations of specific primers. Relative changes in gene expression were calculated using the 2-ddCt method. Western blots were used to measure the protein expression (4 replicates). In addition, plasma NO and CO levels were determined by spectrophotomety. Non-parametric tests were used to find statistical meaning. The Mann-Whitney U-test was applied to establish differences between the analysed groups. In addition, the Wilcoxon test for paired data was used to study the evolution of the intra-group values. Lung ischemia reperfusion (I/R) significantly increased both mRNA and protein expression of TNFa (p<0.01), IL-1 (p<0.05) and MCP1 (p<0.05). This expression was even higher after 60 minutes of reperfusion (p<0.05). On the contrary, I/R decreased IL10 expression (p<0.05). Lung I/R decreased eNOS expression (p<0.05) and this effect was accompanied by a decrease in plasma NO levels (p<0,01). These effects were blocked by lidocaine. No changes were observed in CO levels. These results suggest that lidocaine prevents I/R-induced lung injury through the reduction of proinflammatory cytokines. The administration of lidocaine might be a prospective management for preventing lung injury secondary to I/R.