We observed changes of intermedin (IMD) and its receptor system mRNA expressed with renal ischemia/reperfusion (I/R) injury in the rat and explored the protective effects of IMD pretreatment on renal injury. In comparison with sham group kidneys, I/R-injured rats had severe pathological changes; renal superoxide dismutase (SOD) was decreased ( 34.8%) and tissue malondialdehyde (MDA) was increased (+34%; both p<0.01); renal IMD content and mRNA levels were decreased by 63.5% and 48.2%, respectively (both p<0.01); and CRLR, RAMP1, and RAMP3 mRNA levels were decreased by 39.5%, 11.2%, and 21.2%, respectively (all p<0.01). After pretreatment with IMD (1.0 and 5.0 nmol/kg) and ADM (5.0 nmol/kg), MDA content was lowered by 49.2%, 37.3%, and 36.9% respectively (all p<0.01) and SOD activity was increased by 37.2%, 22.1%, and 19.7%, respectively (all p<0.01). Thus, renal I/R injury in rat downregulated IMD and its receptor system and pretreatment with IMD attenuated I/R-induced renal functional and structural damage. We observed changes of intermedin (IMD) and its receptor system mRNA expressed with renal ischemia / reperfusion (I / R) injury in the rat and explored the protective effects of IMD pretreatment on renal injury. Both renal IMD content and mRNA levels were decreased by 63.5% -injured rats had severe pathological changes; renal superoxide dismutase (SOD) was decreased (34.8%) and tissue malondialdehyde (MDA) was increased (all p <0.01); and CRLR, RAMP1, and RAMP3 mRNA levels were decreased by 39.5%, 11.2%, and 21.2%, respectively MDA content was increased by 49.2%, 37.3%, and 36.9% respectively (all p <0.01) and SOD activity was increased by 37.2%, 22.1%, and 19.7%, respectively respectively (all p <0.01). Thus, renal I / R injury in rat downregulated IMD and its receptor system and pretreatment with IMD attenuated I / R-induced renal functional and structural damage.