Objective To study the molecular mechanism of ligustilide (LIG) in HUVEC injury induced by ox?LDL. Methods HUVECs were randomly divided into five groups: control group (untreated cells), model group (cells treated with 100 μmol/ L ox?LDL for 24 h), and LIG groups (cells pre?treated with 10, 20, or 40 μmol/ L LIG for 2 h and then exposed to 100 μmol/ L ox?LDL for 24 h). Cell viability was measured by CCK8 assays. Levels of inflammatory cytokines TNF?α and IL?6, and ICAM?1 and VCAM?1 were assayed by ELISAs. mRNA levels of TNF?α, IL?6, ICAM?1, VCAM?1, and miR?181b were determined by qRT?PCR and the protein level of NF?κB by Western blotting. Results Compared with the control group, ox?LDL induced apoptosis and inflammatory cytokine secretion in HUVECs ( P <0.01). LIG protected cells and reduced apoptosis. Moreover, LIG reduced the secretion of inflammatory cytokines compared with the model group ( P < 0.01). LIG also upregulated miR?181b expression and downregulated its target gene, NF?κB. Inhibition of miR?181b mostly reduced the effect of LIG on inflammation in HUVECs. Conclusions LIG reduces damage by ox?LDL in HUVECs, partly through inhibiting expression of NF?κB via miR?181b to reduce the inflammatory reaction induced by ox?LDL.