A medical hydrogel microsphere system was developed to balance immune homeostasis and promote diabetic wound healing. The system balances JAK/STAT signaling, fostering positive communication between dead and live cells. miR-20a-5p may be involved in modulating JAK/STAT signaling. The optimized system shows potential in promoting diabetic wound therapy. Adipose stem cell-derived apoptotic bodies (ADSC-ABs) regulate immunity and have shown potential for immunomodulation and regeneration in diabetic wound therapy. However, their local application has been limited by unclear regulatory mechanisms, rapid clearance, and short tissue retention times. To address these issues, ADSC-ABs were encapsulated in methacrylate-anhydride gelatin (GelMA) microspheres (GMSs) for controlled release. The ABs@GMSs system was evaluated in a diabetic rat wound model and showed good biocompatibility, significantly delayed local clearance of ABs, and ameliorated diabetic wound inflammation and promoted vascularization, thus facilitating healing. The study reveals the regulatory mechanism of ADSC-ABs in balancing macrophage inflammatory polarization and highlights the importance of delaying their local clearance by GMSs. These findings have important implications for the development of novel therapies for diabetic wound healing. The study also identified miR-20a-5p as a potential effector in promoting diabetic wound recovery. The ABs@GMSs system effectively balanced macrophage polarization through the JAK-STAT pathway, mediated by miR-20a-5p. The system showed improved retention of ABs at the wound site compared to free ABs, leading to enhanced wound healing. The results suggest that ABs@GMSs can modulate macrophage polarization, reduce inflammation, and promote angiogenesis and collagen deposition, which are critical for wound healing. The study demonstrates that ABs@GMSs can effectively balance macrophage polarization and promote wound healing in diabetic wounds. The findings highlight the potential of ABs@GMSs as a novel strategy for balancing macrophage polarization through the JAK-STAT signaling pathway, which holds great promise for achieving inflammatory homeostasis and facilitating wound healing in chronic diabetic wounds.A medical hydrogel microsphere system was developed to balance immune homeostasis and promote diabetic wound healing. The system balances JAK/STAT signaling, fostering positive communication between dead and live cells. miR-20a-5p may be involved in modulating JAK/STAT signaling. The optimized system shows potential in promoting diabetic wound therapy. Adipose stem cell-derived apoptotic bodies (ADSC-ABs) regulate immunity and have shown potential for immunomodulation and regeneration in diabetic wound therapy. However, their local application has been limited by unclear regulatory mechanisms, rapid clearance, and short tissue retention times. To address these issues, ADSC-ABs were encapsulated in methacrylate-anhydride gelatin (GelMA) microspheres (GMSs) for controlled release. The ABs@GMSs system was evaluated in a diabetic rat wound model and showed good biocompatibility, significantly delayed local clearance of ABs, and ameliorated diabetic wound inflammation and promoted vascularization, thus facilitating healing. The study reveals the regulatory mechanism of ADSC-ABs in balancing macrophage inflammatory polarization and highlights the importance of delaying their local clearance by GMSs. These findings have important implications for the development of novel therapies for diabetic wound healing. The study also identified miR-20a-5p as a potential effector in promoting diabetic wound recovery. The ABs@GMSs system effectively balanced macrophage polarization through the JAK-STAT pathway, mediated by miR-20a-5p. The system showed improved retention of ABs at the wound site compared to free ABs, leading to enhanced wound healing. The results suggest that ABs@GMSs can modulate macrophage polarization, reduce inflammation, and promote angiogenesis and collagen deposition, which are critical for wound healing. The study demonstrates that ABs@GMSs can effectively balance macrophage polarization and promote wound healing in diabetic wounds. The findings highlight the potential of ABs@GMSs as a novel strategy for balancing macrophage polarization through the JAK-STAT signaling pathway, which holds great promise for achieving inflammatory homeostasis and facilitating wound healing in chronic diabetic wounds.