Objective To investigate the effect of protease inhibitor H89 on the morphology of the Golgi apparatus and apoptosis after oxygen-glucose deprivation followed by reperfusion (OGD/R) in neurons.Methods HT22 hippocampal neurons from mice cultured in vitro were divided in to control group, model group, and H89 intervention group. The cells in the model group and the H89 intervention group were further divided into 6-hour, 12-hour, and 24-hour subgroups according to the time point of reperfusion. MTT assay was used to measure cell viability; Hoechest33258 fluorescence staining was used to evaluate cell apoptosis; cell immunofluorescence was used to observe the morphology of the Golgi apparatus; Western blot was used to measure the expression of GM130 and GAAP proteins.Results Compared with the model group, the H89 intervention group had a significant increase in the viability of HT22 cells (P<0.05), and there was a significant difference between the 12-hour subgroups of the H89 intervention group and the model group (OD=0.1467±0.0090, P<0.05). Compared with the model group, the H89 intervention group had a reduction in cell apoptosis rate (P>0.05). At 6 and 12 hours, the H89 intervention group had a slight reduction in the degree of fragmentation of the Golgi apparatus compared with the model group. The H89 intervention group had similar expression of GM130 as the model group (P>0.05), and compared with the model group, the H89 intervention group a significant increase in the expression of GAAP at 24 hours (gray level ratio=0.4066±0.0288, P<0.05).Conclusions H89 intervention cannot alleviate Golgi fragmentation and cell apoptosis after OGD/R.