Objective To investigate the mechanism by which crocin alleviates high glucose-induced glomerular endothelial cell damage based on the inhibitor of nuclear factor kappa B kinase β （IKKβ）/nuclear transcription factor-κB （NF-κB） signaling pathway. Methods High glucose-induced human glomerular endothelial cells were treated with crocin at concentrations of 0， 12.5， 25， 50， and 75 μmol/L， and the optimal concentration of crocin was screened via the CCK-8 experiment. Glomerular endothelial cells were randomly assigned to the normal group， osmotic pressure control group， high glucose group， crocin group， phorbol ester （PMA） group， and crocin + PMA group. Except for the normal group and osmotic pressure control group， all the other groups were induced with high glucose and treated with crocin and the IKKβ/NF-κB signaling pathway activator PMA according to different groups for 48 hours. Immunofluorescence staining was employed to observe the cytoskeleton of the cells. The CCK-8 experiment， Transwell experiment， and TdT-mediated dUTP nick end labeling （TUNEL） staining were carried out to detect cell viability， permeability， and apoptosis， respectively. The oxidative stress and inflammation-related factors in the cells were measured. Western blot （WB） was utilized to detect the expression of proteins related to apoptosis， tight junctions， and the IKKβ/NF-κB signaling pathway. Results Compared with the normal group and the osmotic pressure control group， the high-glucose group exhibited a decrease in the activity of glomerular endothelial cells， the activities of superoxide dismutase （SOD） and glutathione peroxidase （GSH-Px）， the relative expression of occludin protein， and the relative expressions of zonula occludens-1 （ZO-1） and Bcl-2 protein （P < 0.05）. Meanwhile， it showed an increase in permeability， apoptosis rate， malondialdehyde （MDA） content， interleukin （IL）-6 and IL-1β levels， the relative expression of Bax protein， and the ratios of p-IKKβ/IKKβ， p-IκB-α/IκB-α， and p-NF-κB p65/NF-κB p65 （P < 0.05）. Compared with the high-glucose group， the crocin group showed an increase in the activity of glomerular endothelial cells， the activities of SOD and GSH-Px， the relative expression of occludin protein， and the relative expressions of ZO-1 and Bcl-2 protein （P < 0.05）. In addition， it had a decrease in permeability， apoptosis rate， MDA content， IL-6 and IL-1β levels， the relative expression of Bax protein， and the ratios of p-IKKβ/IKKβ， p-IκB-α/IκB-α， and p-NF-κB p65/NF-κB p65 （P < 0.05）. The trend of changes in various indicators in the PMA group was opposite to that in the crocin group （P < 0.05）. Compared with the crocin group， the crocin + PMA group showed a decrease in the activity of glomerular endothelial cells， the activities of SOD and GSH-Px， the relative expression of occludin protein， and the relative expressions of ZO-1 and Bcl-2 protein （P < 0.05）. Moreover， it presented an increase in permeability， apoptosis rate， MDA content， IL-6 and IL-1β levels， the relative expression of Bax protein， and the ratios of p-IKKβ/IKKβ， p-IκB-α/IκB-α， and p-NF-κB p65/NF-κB p65 （P < 0.05）. Conclusion Crocin alleviates the damage to glomerular endothelial cells induced by high glucose by inhibiting the activation of the IKKβ/NF-κB signaling pathway.