Diabetic foot ulcer (DFU) is a common complication of chronic diabetes mellitus. Oxygen plays a critical role in the healing process of DFU wounds by promoting cell migration and neovascularization. However, clinical hyperbaric oxygen (HBO) therapy predominantly uses systemic oxygen administration, posing challenges in inadequate DFU local oxygen penetration and potential ectopic organs oxygen toxicity. To address these challenges, a strategy to encapsulate oxygen with lipid microbubbles (OMBs) and incorporate them into a body temperature-sensitive heparin-pluronic copolymer hydrogel (HP/OMBs) have been developed. HP/OMBs showed high biocompatibility both in vitro and in vivo. After in situ administration, oxygen can be released from HP/OMBs to the local deep site of the DFU wounds under ultrasound (US) triggering. Thus, given its biocompatibility and practicality, the combined action of HP/OMBs and the US has important translational value in accelerating diabetic chronic wound healing.