- Caffeic acid phenethyl ester (CAPE) is considered as one of the most active components of Propolis extract (PE), a natural product obtained from beehives. PE comprises a complex of chemicals and has been found to have various biological activities. The aim of the present study is to assess the antibacterial activities CAPE has against various gram positive [gram (+)] and gram negative [gram (-)] bacteria and try to elucidate its mechanism of action. Bacteria were grown in the presence of various doses of CAPE and examined at different periods of time for their growth, both by absorbance (OD) measurement and colony assay. The results show that CAPE significantly inhibited the growth of most examined gram (+) bacteria while having only a slight inhibitory effect on most tested gram (-) bacteria. Our results also show that continuous treatment of gram (+) bacteria with CAPE for at least 6h caused irreversible inhibition of the bacterial growth (bacteriocidic effect); however, treatment for shorter periods of time caused only a stopping of bacterial growth (bacteriostatic effect). It seems that these effects were caused, at least partially, as a result of disruptions of the treated bacterial outer and plasma membranes. There is no significant synergistic effect between CAPE and ampicillin, although an additive effect has been found.