AIM: To investigate the release of cyclodextrin-5-amino salicylic acid (CyD-5-ASA) in cecum and colon.METHODS: An anti-inflammatory drug 5-ASA was conjugated onto the hydroxyl groups of α-, β- and γ-cyclodextrins (CyDs) through an ester linkage, and the in vivo drug release behavior of these prodrugs in rat s gastrointestinal tract after the oral administration was investigated.RESULTS: The 5-ASA concentration in the rats stomach and small intestine after the oral administration of CyD5-ASA conjugate was much lower than that after the oral administration of 5-ASA alone. The lower concentration was attributable to the passage of the conjugate throughthe stomach and small intestine without significant degradation or absorption, followed by the degradation of the conjugate site-specific in the cecum and colon. The oral administration of CyD-5-ASA resulted in lower plasma and urine concentration of 5-ASA than that of 5-ASA alone.CONCLUSION: CyD-5-ASA conjugates may be used as prodrugs for colon-specific drug delivery system.