This study presents an injectable hydrogel delivery system designed to enhance the duration and effectiveness of local anesthesia. The system combines heterogeneous microspheres loaded with ropivacaine (ROP) and an injectable self-healing gel matrix made from carboxymethylcellulose (CMC-ADH) and oxidized hyaluronic acid (OHA). The microspheres, prepared using a microfluidic chip and in situ alkalization, achieve a drug loading capacity of 41.1% with a drug release time of over 160 hours in vitro. The gel matrix, with a gelation time of less than 30 seconds, forms a stable reservoir for the microspheres, providing long-term retention and controlled drug release. The combination of ROP and dexmedetomidine (DEX) in the gel matrix enhances the synergistic analgesic effects, achieving sensory and motor blockade times of 48 and 36 hours, respectively, in vivo. The system demonstrates good biodegradability, tissue compatibility, and reduced cytotoxicity, making it a promising strategy for long-acting postoperative pain management.This study presents an injectable hydrogel delivery system designed to enhance the duration and effectiveness of local anesthesia. The system combines heterogeneous microspheres loaded with ropivacaine (ROP) and an injectable self-healing gel matrix made from carboxymethylcellulose (CMC-ADH) and oxidized hyaluronic acid (OHA). The microspheres, prepared using a microfluidic chip and in situ alkalization, achieve a drug loading capacity of 41.1% with a drug release time of over 160 hours in vitro. The gel matrix, with a gelation time of less than 30 seconds, forms a stable reservoir for the microspheres, providing long-term retention and controlled drug release. The combination of ROP and dexmedetomidine (DEX) in the gel matrix enhances the synergistic analgesic effects, achieving sensory and motor blockade times of 48 and 36 hours, respectively, in vivo. The system demonstrates good biodegradability, tissue compatibility, and reduced cytotoxicity, making it a promising strategy for long-acting postoperative pain management.