Objective：To investigate the protective effect and mechanism of nicotine on cold ischemia reperfusion injury in rats. Methods：Totally 30 male SD rats were randomly divided into sham operation group，IRI group and nicotine groups（40，400，4 000 ?滋g/kg），6 rats in each group. The left renal ischemia-reperfusion injury model was set up in IRI group，and the right kidney was removed. The right kidney was removed only in the sham operation group. The nicotine groups injected nicotine into the abdominal cavity before closing it，while the rest were the same as those in the IRI group. The concentrations of serum creatinine and blood urea nitrogen were determined by colorimetric method. The concentrations of interleukin-1 β（IL-1β） and tumor necrosis factor-α（TNF-α） in serum were detected by ELISA. The concentrations of nuclear factor κB（NF-κB） in cell nucleus were detected by Western blot and method of SP immunohistochemistry. HE staining was performed to observe the pathological changes of renal tissue. Results：IRI can cause pathological changes of kidney in rats，increase the level of serum creatinine（P=0.005） and blood urea nitrogen（P=0.003），increase the level of NF-κB p65（P=0.002） in the nucleus of renal tubular epithelial cells，and increase serum TNF-α（P=0.011） and IL-1β（P=0.007）. Compared with those in IRI group，the intraperitoneal injection of nicotine can reduce the content of NF-κB p65（P=0.003） in the nucleus of renal tubular epithelial cells，reduce the level of serum creatinine（P=0.005），blood urea nitrogen（P=0.004），TNF-α（P=0.009） and IL-1β（P=0.007）. But there was no significant difference between the three dose groups. Conclusion：Nicotine has protective effect on renal ischemia reperfusion injury，and its mechanism may be related to the inhibition of the nucleation of NF-κB p65 in renal tubular epithelial cells，reducing the inflammatory reaction and reducing the level of TNF-α and IL-1β.