Many studies have demonstrated the cytoprotective effects of hydrogen sulfide (H(2)S) in vitro and/or in vivo ischemic injury. The aim of the current study was to investigate whether exogenous H(2)S attenuates the neuronal injury induced by brain ischemia. As an H(2)S donor, sodium hydrosulfide (NaHS) was administered intraperitoneally (5.6 mg/kg/day, i.p.). The effects of exogenous H(2)S on neurons of ischemic hippocampus were examined by using measurement of behavior, electrophysiology, morphology and immunohistochemical staining, respectively. Our results showed that exogenous H(2)S significantly improved spatial learning and memory deficits induced by brain ischemia (P < 0.01). Exogenous H(2)S enhanced synaptic plasticity in the hippocampus of brain-ischemic rats, inhibited the edema around pyramidal neurons and the nuclear shrink induced by ischemia, and promoted the expression of growth-associated protein-43 (GAP-43) in the CA1 region of hippocampus post ischemia. The results suggest a protective effect and therapeutic potential of H(2)S in the treatment of brain ischemia.