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There is an urgent need for more efficient inflammation\u2010targeting strategies to improve therapeutic effect and reduce systemic drug exposure. Herein, an oxidation\u2010responsive metal\u2013organic framework material (Ce\u2010MOF@PSS) is reported that preferentially adheres to inflamed intestine via enema. The overproduced reactive oxygen species (ROS) at inflammatory sites induces transformation of Ce\u2010MOF@PSS from mesopore to macropore with local drug release. In experimental colitis, the Ce\u2010MOF@PSS delivery system exhibits excellent inflammation\u2010targeting efficacy and superior therapeutic effect over free drug on suppressing inflammation and repairing intestinal barrier function. 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