Abstract: 【Abstract】 Objective To investigate the role of Capsaicin sensitive C fibers (CapsCF) denervation in lung ischemia-reperfusion (IR) injury and the possible mechanism related to oxidative stress. Methods Thirty two male New Zealand rabbits were randomized into four groups: IR group (IR), sham group (S), capsaicin pretreated IR group (CIR), and capsaicin pretreated sham group (CS). The rabbits in CIR and CS groups were pretreated with capsaicin (100mg/kg) to induce functional ablation of CapsCF, and then subjected to lung ischemia and reperfusion. The rabbits in IR group were not treated with capsaicin before lung ischemia and reperfusion. Thereafter, blood samples and lung tissue samples were obtained for blood gas and biochemical analyses, including the measurements of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT). The lung wet/dry weight ratio and histopathological changes were also assessed. Results Compared to S and CS group, partial pressure of oxygen (PO₂) values in IR and CIR groups significantly decreased (P<0.05). In contrast, the alveolar-arterial oxygen gradient (A-aDO₂), lung wet/dry weight ratio increased in IR and CIR groups (P<0.05). Capsaicin pretreatment in CIR group increased lung wet/dry weight ratio and lung pathologic lesions, along with higher level of MDA and lower activity of SOD and CAT (P <0.05, vs. IR). Conclusion Denervation of CapsCF aggravated lung ischemia-reperfusion injury of rabbits, which seems to be closely related to the excerbation of oxidative stress.