Secondary burn necrosis is the expansion and deepening of the original burn injury several days after injury. Limiting the extent of secondary burn necrosis may improve outcomes. In this study, we examined the ability of the lipid mediator of inflammation-resolution resolvin D2 (RvD2) and chromatin-lysing enzyme (DNase) to reduce secondary burn necrosis. Male Wistar rats were injured using a brass comb with 4 prongs heated in boiling water. This method created 2 parallel rows of 4 rectangular burned areas separated by 3 unburned interspaces. Starting at 2 hours after the burn injury, rats received either 25 ng/kg RvD2 intravenously daily for 7 days or 200 U/kg DNase every 12 hours for 3 days. We documented the necrosis around the initial wounds by digital photography. We used laser Doppler to assess the total blood flux in the burn area. We evaluated the functionality of the capillary network in the interspaces by optical coherence tomography angiography. We performed histological examination of wound skin tissue samples collected at 14 days postburn. We found that the interspace areas were preserved and had higher blood flow in the RvD2-treated group, while the burn areas expanded into the interspace areas, which were confluent by 7 days postburn, in the control-untreated group. We found a larger monocyte-to-neutrophil ratio in the RvD2-treated group compared with the DNase-treated and control groups (P < .05). Overall, RvD2 suppresses secondary necrosis and starts regeneration, highlighting the role of inflammation resolution as a potential therapeutic target in burn care.