Aim To investigate the associations of serum interleukin-18 (IL-18) and C-reactive protein (CRP) with endothelial dysfunction in patients with essential hypertension. Methods Flow-mediated dilation (FMD) in right brachial artery was detected to reflect endothelial function by ultrasound. Serum IL-18 and CRP levels were also assayed. Bivariate correlation analysis was applied to show the correlation of serum IL-18 and CRP levels with FMD. Multiple linear regression was performed followed by unconditional logistic regression. Results The serum IL-18 and CRP levels were significantly higher in essential hypertension group than those in control group (P<0.01), but the FMD was significantly lower (P<0.01). In patients with essential hypertension, with the degree of blood pressure ascending, the serum IL-18 and CRP levels climbed gradually, but the FMD was descending (P<0.05). The serum IL-18 and CRP levels were significantly increased in FMD abnormal subgroup in comparison with those in FMD normal subgroup (P<0.01). Serum IL-18 and CRP levels were negatively correlated with FMD, respectively (P<0.01). In stepwise multiple linear regression model, after adjustion with other factors, the correlations of IL-18 and CRP levels with FMD persisted, respectively. The relationship between FMD and other study factors were analyzed by non-conditional logistic stepwise regression. Serum IL-18 and CRP levels were the important independent risk factors for FMD abnormal. Conclusions Serum IL-18 and CRP were negatively correlated with endothelial dysfunction in patients with essential hypertension, and the correlations persisted after adjustion with other factors, respectively. Serum IL-18 and CRP were the important independent risk factors for carotid artery plaque. The study suggests the link between inflammation and endothelial dysfunction in patients with essential hypertension.