Background: Propolis is a product of honeybees that contains a variety of different compounds, including caffeic acid phenethyl ester (CAPE). Propolis and its bioactive compounds are widely used in folk medicine and as a dietary supplement. Previously it has been shown that CAPE has antioxidant, anti-inflammatory, antimicrobial, antiviral, immunomodulatory, and anticancer activity. Objective: This in vitro study was designed to investigate the vasoactive effects of CAPE on quiescent and precontracted human umbilical arteries. Methods: Umbilical artery strips were suspended in aerated organ baths containing a buffer solution. The strips were randomly allocated to study groups (n=8). Via a transducer and computer, changes in isometric tension were recorded. The effects of cumulative CAPE (10-8-10-4M) on basal tone of the artery, and in different groups of strips, the vasodilatory effect of cumulative CAPE on the constriction elicited by endothelin (ET-1), prostaglandin F2α (PGF2α) and U46619, and the effect of incubation with NO synthase inhibitor L-NAME, were recorded. Conclusion: CAPE elicits concentration-dependent relaxation on precontracted human umbilical artery strips depending on the constrictor agent. NO plays significant role in CAPE’s vasorelaxant effect.