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 activities.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 the 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. Results: CAPE did not alter the basal tone (p>0.05). CAPE caused significant concentration-dependent relaxation in strips precontracted with both ET-1 and PGF2α (p<0.05) (contraction Emax with 10-4M CAPE = %73.65±12.17 and %79.83±7.20 respectively). L-NAME inhibited these relaxation responses elicited by CAPE (p<0.05). Only the lowest concentration of CAPE (10-8M) caused significant relaxation with U46619 (p<0.05) (contraction Emax with 10-8M CAPE = %90.23±3.19). L-- NAME completely inhibited this relaxation response (p<0.05). Conclusion: CAPE elicits concentration-dependent relaxation on precontracted human umbilical artery strips depending on the constrictor agent. NO plays a significant role in CAPE’s vasorelaxant effect.