Background Caffeic acid phenethyl ester (CAPE), an active component of propolis, has been proven to have anti-inflammatory and antiallergic properties. We have investigated the activity of CAPE in regulating cytokine-induced eotaxin production and its related signal protein, signal transducer and activator of transcription 6 (STAT6), in human lung fibroblast. Methods The CCD-11Lu human lung fibroblast cell line was used as an in vitro model. Cells were pretreated with CAPE followed by stimulation with interleukin-4 and tumor necrosis factor alpha. The levels of eotaxin in cultured supernatants were measured by enzyme-linked immunosorbent assay. The amounts of STAT6 and phosphorylated STAT6 in cellular nuclear protein extracts were determined by Western blot analysis. STAT6 DNA binding activities were detected by electrophoretic mobility shift assay. Results Pretreated CCD-11Lu cells with noncytotoxic doses (0.1–10 μM) of CAPE inhibited the production of eotaxin under stimulation of interleukin-4 (10 ng/mL) and tumor necrosis factor alpha (10 ng/mL). CAPE pretreatment also decreased the amount of phosphorylated STAT6 and the STAT6 DNA binding complexes in nuclear extracts. Conclusion CAPE inhibited the production of eotaxin protein in stimulated human lung fibroblast cells in a dose-dependent manner. This activity is, at least, through STAT6 inhibition. We suggest that CAPE is a promising agent in controlling eotaxin secretion and subsequent eosinophils influx and may therefore have a potential role to play in treating allergic airway disease.