<p>CD200 is a transmembrane glycoprotein, which has an anti-inflammatory effect through interaction with CD200 receptor 1 and inhibits the NF-κB pathway associated with loss of barrier function. In this study, CD200 was fused with the Fc domain of IgG to generate recombinant human CD200-Fc. The CD200-Fc was produced in the transgenic <i>Nicotiana tabacum</i> plant by <i>Agrobacterium</i>-mediated transformation. Genomic DNA PCR and RT-PCR analyses verified the successful insertion of transgene and transcription of CD200-Fc mRNA in the leaves of the plant transformants, respectively. Immunoblot analysis confirmed expression of CD200-Fc in the transgenic plant. The plant-derived CD200-Fc (CD200-Fc^P) was successfully purified by affinity chromatography. The qRT-PCR and immunoblot analyses confirmed that mRNA and protein levels of Zonula occludens-1, a tight junction protein for barrier protection, increased in TCCSUP bladder epithelial cells treated with CD200-Fc^P. These results suggest that CD200-Fc expressed in a plant system could exert beneficial effects on diseases with barrier dysfunction such as interstitial cystitis by regulating Zonula occludens-1 expression in bladder epithelial cells.</p>