The present study aimed to investigate the effect of the expression of interleukin (IL)-18 and related markers on deep venous thrombosis (DVT) to examine their correlation. Sprague-Dawley rats of different models were established and were randomly assigned into three groups. The expression of IL-18, nuclear factor (NF)-kappa B and von Willebrand factor (vWF) were detected in blood samples. The inferior vena cava (IVC) was ligated to establish the DVT model. Rat IL-18 overexpression and inhibition vectors were constructed. The expression levels of IL-18 and related markers in the venous wall were compared between the model group and the control group using reverse transcription-quantitative polymerase chain reaction and western blot analyses. Following the culture of human umbilical vein endothelial cells (HUVECs), IL-18 was added to the cells, following which the growth of the HUVECs, and changes in vWF and other endothelial functional markers were analyzed. The IVC model demonstrated complete thrombosis at 8 h and stable thrombosis at 24 h. At 24 h following model establishment, the expression levels of IL-18, NF-kappa B and vWF were high in the blood samples with the occurrence and development of thrombosis (P<0.05). The weight, length and weight/length ratio of thrombi in each model group showed significant differences from those in the control group (P<0.05) with the overexpression of IL-18, and the expression levels of NF-kappa B and vWF in venous tissues were altered with abnormal expression levels of IL-18. IL-18 damaged HUVECs and significantly increased viability in early-stage apoptosis, promoted the upregulation of vWF and P-selectin, and reduced tissue plasminogen activator. IL-18 and the related markers were closely associated with the occurrence and development of DVT.