Background NF-B plays a key role in ischemia reperfusion injury (IRI). Systemic inhibition of NF-B by various methods has been proven to ameliorate IRI. However, NF-B is also responsible for tissue protection against IRI. Systemic NF-B inhibition may not be the optimal way for preventing IRI because of its complex roles. T cells are essential in mediating IRI. NF-B is an important molecule during T cell activation. It is not clear the effect of T cell-specific NF-B inhibition on IRI. We aimed to study the effect of T cell-specific NF-B inhibition on renal IRI in IBN-Tg mice. We also compared the different effects between T cell-specific and systemic NF-B inhibition on IRI. Methods Renal IRI was induced by left renal pedicle clamping for 60 or 80 min in wild-type, ursolic acid-treated or IBN-Tg mice. Renal function, histologic examination and overall survival after lethal IRI was evaluated in each group. Results Serum creatinine, BUN, and pathologic damage were all reduced in IBDN-Tg mice and ursolic acid-treated mice than those in the control group. All the above indexes were improved better in IBDN-Tg mice than those in ursolic acid-treated mice. The survival rate of IBDN-Tg mice was higher than that of ursolic acid-treated mice after lethal kidney ischemia reperfusion injury. Immunohistochemistry showed a significant reduced CD4+ T cells and neutrophil infiltration in IBDN-Tg mice. Conclusion T cell-specific NF-B inhibition provides powerful protective effect against renal IRI.