Background: 10-15% of direct maternal death caused by preeclampsia and eclampsia. Almost 30% of maternal death in Indonesia caused by Hypertension in pregnancy Pathogenesis of preeclampsia characterized by increase of HIF-1α placenta expression in hypoxia and ischemia condition that leading producer of IL6 by endothelial cells, phagocyte cells, macrophage, mast cells and also fibroblast as an immunologic maladaptation response. The endothelial dysfunction also causing major producer of endhotelin-1 that induced production of IL-6 and TNFα as an inflammation response by activating Nfkβ. Black seed as known as black cumin (Nigella sativa) with Thymoquinone and thymol as the active substances is a potential in prevention and therapy for preeclampsia. Black seed act as anti-inflammatory scavenger and inhibit the activation of NF-kB and therefore reduces expression of IL-6 and TNFα and also the symptoms of preeclampsia. Objective: To determine the effect of black seed ethanol extract on the expression of IL-6 and TNFα in Huvecs model exposed by preeclamptic plasma. Methods: The trial study with post-test only control group design using Huvecs model exposed by preeclamptic plasma were randomly divided into six groups. The control group was Huvecs model exposed by normal pregnancy plasma. The Positive control group using Huvecs model exposed by preeclamptic plasma While the four treatment groups using Huvecs model exposed by preeclamptic plasma received treatment of ethanol extract of black seed with doses of 50, 100, 200, and 400 ppm. Then all the groups were moved to tissue culture well with gelatin covering cover glass inside incubated for 20 minutes Continued by examination of the expression of IL-6 and TNFα in endothelial cells using immunohistochemical staining. Results: Data were analyzed using one way ANOVA test to compare the mean of TNFα and IL6 expression, and it showed significant influence of ethanol extract of black seed in various doses to decrease the expression of TNFα and IL6 expression of Huvecs model exposed by preeclampsia plasma. The optimal dose in both is 100 ppm. Conclusion: The black seed ethanol extract administration decreases the expression of TNFα and IL6 expression in Huvecs model exposed by preeclampsia plasma.