Objective：To investigate the activation of p38 signaling transduction cascade in renal ischemia reperfusion injury(IRI) and to study the effect of tempol, a free oxygen radical scavenger, on p38 activation. Methods：Male SpragueDawley rats were randomly divided into shamoperation group (n=10), IRI group (n=45) and IRI + tempol group(n=10). Animal IRI model was created by renal pedicle ligation (50 min) of the left kidney along with a contralateral nephrectomy followed by 2 h reperfusion. Rats were sacrificed on 0, 5, 10, 15, 30, 45 min, 1 and 2 h after renal reperfusion. Animals in IRI + tempol group were pretreated with tempol (100 mg/kg) 1 h before undergoing the same protocol as in IRI group; the kidney was harvested after 45 min of reperfusion. Animals in the shamoperation group were subjected to contralateral nephrectomy without renal pedicle ligation and were sacrificed 45 min later. The renal p38 activities of the 3 groups were determined by Western blotting analysis. Malondialdehyde (MDA) content was detected and proinflammatory cytokine TNFα, IL1β levels were analyzed by ELISA. Results： Activation of p38 was observed in the kidney as early as 5 min after reperfusion and reached its peak 45 min after reperfusion and remained to be activated until 2 h after reperfusion（P＜0.05）. The activities of renal p38 in IRI and IRI + tempol group were markedly increased compared with that of the shamoperation group（both P<0.05）. Pretreatment with tempol significantly inhibited IRIinduced p38 activation（P<0.05）; it also decreased MDA activity and TNFα and IL1β levels （both P<0.05）. Conclusion：Our results demonstrate that reactive oxygen speciesmediated p38 activation plays an essential role in IRIinduced renal inflammatory damage in rats, suggesting that inhibition of p38 activation by tempol may be used for prophylaxis and treatment of IRI.