Objective To investigate the neuroprotective effect of soyasaponin Bb ( SSBb) pretreatment in cerebral ischemia / reperfusion ( I/ R) rats. Methods SD rats were divided into sham, model, and low- and high-dose SSBb pretreatment groups with 15 rats each. A rat model of middle cerebral artery occlusion (MCAO) was established by suture occlusion, and reperfusion was performed 2 h after occlusion to simulate brain I/ R. Low- and high-dose SSBb pretreatment groups were administered 20 and 50 mg / kg SSBb by gavage, respectively, at 1 h before MCAO. At 24 h after reperfusion, neurological deficits were assessed by the modified neurological severity score, and cerebral infarct volume was measured by 2,3,5-triphenyltetrazolium chloride staining. Microtubule-associated protein-2 staining was used to assess neuronal damage. Brain water content was measured by the dry / wet weight. Tumor necrosis factor-α (TNF-α) expression in ischemic penumbra was measured by immunofluorescence. Postsynaptic density-95 ( PSD-95 ), synapsin I and synaptotagmin expression was detected by Western blot. Results Compared with the model group, low- and high-dose SSBb pretreatment significantly improved neurological dysfunction, alleviated cerebral edema and cerebral infarction in MCAO model rats, and decreased expression of TNF-α, PSD-95, synapsin I and synaptotagmin in ischemic penumbra (P<0. 01 or P< 0. 001). The effects in the high-dose group were most significant ( P< 0. 001). Conclusions SSBb pretreatment has a neuroprotective effect in rats with cerebral I/ R injury.