〔Abstract〕 Objective To investigate the antioxidant and neuroprotective effects of morroniside on hypoxic ischemic brain injury(HIBI) model rats and its possible mechanism. Methods Rice method was used to establish HIBI rat model. Rats were randomly divided into 6 groups: Control group, model group, Morroniside(25, 50, 100 mg/kg) group and Nimodipine group. The first two groups were given normal saline by gavage, and the last four groups were given corresponding doses of Morroniside and nimodipine, once every day for 28 consecutive days.The cerebral nerve function of rats was scored and the cerebral water volume was measured.HE staining was used to observe the histopathological changes of rat brain tissue. The levels of malondialdehyde(MDA), lactate dehydrogenase(LDH) and superoxide dismutase(SOD) in rat brain tissue were measured by ELISA. The protein expression levels of B cell lymphoma-2(Bcl-2),Bcl-2 associated X protein(Bax), Caspase-3, Caspase-9, brain-derived neurotrophic factor(BDNF), basic fibroblast growth factor(bFGF), synaptophysin(SYP), postsynaptic density-95(PSD95), transcription factor nuclear factor erythroid 2(NF-E2)-related factor 2(Nrf2) and heme oxygenase 1(HO-1)in brain tissue were detected by Western blot. Results Compared with the model group, the neurological function score and hydrocephalus volume of rats in Monoside treatment group decreased(P<0.01), the pathological damage degree of brain tissue improved, Bcl-2 increased, Bax, Caspase-3 and Caspase-9 decreased(P<0.01), and SOD activity increased(P<0.01), LDH and MDA content decreased(P<0.01). In addition, the expressions of bFGF, BDNF, PSD95, SYP and antioxidant pathway proteins Nrf2 and HO-1 were up-regulated(P<0.01). Conclusion Monoside has antioxidant and neuroprotective effects on hypoxic-ischemic brain injury model rats, and its function may be related to the mediating Nrf2 signaling pathway.