Abstract: AIM　To explore whether dexamethasone-dextran (260 000) has the characteristics of site-specific delivery in rat gastrointestinal tract. METHODS　Dexamethasone prodrug and dexamethasone were administered to rat ig at the dose of 5 μmol·kg^-1. The distribution of dexamethasone in the contents and mucosa of different parts of the rat GI tract at different time intervals and its concentration in plasma were determined by HPLC. RESULTS　Dexamethasone was mainly released in the cecum and colon contents and mucosa after oral administration of dexamethasone prodrug. The absorption was reduced significantly. The peak time of the drug in plasma was 8.1 h, and the peak concentration was 32 μg·L^-1. However, free dexamethasone was found mainly in the contents and mucosa of the stomach, proximal and distal small intestine. The peak time of the drug in plasma was 2.2 h, and the peak concentration was 2120 μg·L^-1. CONCLUSION Dexamethasone can be specifically delivered to the large intestine by using dexamethasone-dextran (260 000). It appears that the prodrug has a potential in the treatment of inflammatory bowel disease.