Hydrogen sulphide (H₂S) exerts beneficial effects in myocardial ischaemia (Sivarajah et al. 2006). H₂S is produced in the normal kidney by cystathionine gamma lyase (House et al. 1997), but the role of endogenous H₂S in the pathophysiology of ischaemia/reperfusion (I/R) injury of the kidney is unclear. Here, we have investigated the effects of topical administration of sodium hydrosulphide (NaHS), a H₂S donor, in a rat model of renal I/R injury. Male Wistar rats weighing 200 to 320 g were subjected to 45 min of bilateral renal ischaemia followed by 6 h of reperfusion (under sodium thiopentone (120 mg/kg i.p.) anaesthesia, maintained by supplementary injections (~10 mg/kg i.v.) throughout the experiment) in the absence or presence of NaHS [100 μmol/kg, administered topically as a pre-treatment (15 min) and prior to reperfusion (5 min)]. Administration of NaHS to rats significantly attenuated I/R-induced renal dysfunction (increased serum creatinine), reperfusion injury (increased serum aspartate aminotransferase), glomerular dysfunction (decreased creatinine clearance), and tubular dysfunction (increased fractional excretion of sodium). In addition, Western blot analysis of kidneys taken at the end of the experiment showed that administration of NaHS to rats significantly attenuated Bcl-2, Bid, cyclo-oxygenase-2, inducible nitric oxide synthase and intercellular adhesion molecule-1 when compared to rats subjected to I/R only. These findings suggest that (i) pre-treatment with NaHS protects the rat kidney against I/R injury and (ii) this protective effect may act through anti-apoptotic and anti-inflammatory mechanisms.