Reactive oxygen species have been implicated in pathogenesis injury after ischaemia-reperfusion (I/R). Caffeic Acid Phenethyl Ester (CAPE), an active component of honeybee propolis extract, exhibits antioxidant and anti-inflammatory properties. The aim of this study was to investigate the effects of CAPE on erythrocyte membrane damage after hind limb I/R. Rats were divided into two groups: I/R and I/R with CAPE pre-treatment. They were anaesthetized with intramuscular ketamine 100 mg kg-1. A 4-h I/R period was performed on the right hind limb of all animals. In the CAPE-treated group, animals received CAPE 10 μM by intraperitoneal injection 1 h before the reperfusion. At the end of the reperfusion period, a mid-sternotomy was performed. A 5-ml blood sample was withdrawn from the ascending aorta for biochemical assays. Serum and erythrocyte membrane MDA levels were significantly lower in the CAPE-treated group when compared to the I/R group (p = 0.001 and p < 0.001, respectively). Erythrocyte membrane Na+-K+ ATPases activity in the CAPE-treated group was significantly higher than the I/R group (p < 0.001). In conclusion, CAPE seems to be effective in protecting against oxidative stress. Therefore, we suggest that in order to decrease I/R injury, pre-administration of CAPE may be a promising agent for a variety of conditions associated with I/R. Copyright © 2004 John Wiley & Sons, Ltd.