Prednisolone (PD), a typical glucocorticoid, has been widely used for the treatment of inflammatory bowel disease (IBD). However, when PD is administered orally, a large amount of the drug is absorbed from the upper gastrointestinal (GI) tract and causes systemic side effects. In this study, the anti-inflammatory effect and systemic side effect of the PD succinate/alpha-cyclodextrin (PDsuc/alpha-CyD) ester conjugate after oral administration were studied using IBD model rats. The anti-inflammatory effect of the PDsuc/alpha-CyD conjugate was comparable to those of PD alone. On the other hand, the systemic side effect of the PDsuc/alpha-CyD conjugate was much lower than that of PD alone when administered orally. The lower side effect of the conjugate was attributable to passage of the conjugate through the stomach and small intestine without significant degradation or absorption, followed by the degradation of the conjugate site-specifically in the large intestine. The oral administration of PD alone gave higher plasma concentrations of PD, giving the significant systemic side effect. The results suggested that the PDsuc/alpha-CyD conjugate is useful as a delayed-release type prodrug of PD for colon-specific delivery, owing to alleviation of the systemic side effect, while maintaining the therapeutic effect.