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The management of persistent postoperative pain still remains a clinical challenge currently. Although ropivacaine (RVC) is widely used for postoperative analgesia as a local anesthetic, the short half‐life makes it difficult to achieve the desired duration of analgesia. Herein, a RVC sustained‐release microspheres encapsulated by zeolite imidazole framework‐8 (RVC@ZIF‐8) was synthesized for the first time, which prolonged the sustained‐release of RVC and decreased the resulting drug toxicity. RVC can continuously release in vitro for at least 96 h with high drug loading of 30.6 % and RVC@ZIF‐8 had excellent biocompatibility and low cytotoxicity. In sciatic nerve block model, the sensory block time of RVC@ZIF‐8 was significantly prolonged compared with RVC, achieving more than 72 h post injection and no inflammation or lesion were found. Based on high drug loading, ideal sustained‐release and superior biological safety, RVC@ZIF‐8 will be a novel delivery material for local anesthetic with potential application. [ABSTRACT FROM AUTHOR]