BACKGROUND: Pinocembrin has been widely utilized in clinical settings as a topical treatment for detoxification, inflammation reduction, and healing dermal conditions such as cracked skin and burns. METHODS: In this study, pinocembrin was administered to hypoxia-reoxygenation model in human umbilical vein endothelial cells and 36 rats for 7 days using the McFarlane flap model. Neovascularization was then assessed using Doppler and lead oxide gelatin angiography. Neutrophil infiltration and mean microvessel density were assessed through hematoxylin and eosin staining. Immunofluorescence was employed to assess neovascularization and inflammation by detecting vascular endothelial growth factor, interleukin-1β, interleukin-6, and tumor necrosis factor-α. Pyroptosis was evaluated using western blot analysis. RESULTS: Compared with the control group, the experimental groups exhibited a significant increase in flap survival area with the promotion of neovascularization, mitigation of oxidative stress, and suppression of pyroptosis and inflammation. CONCLUSION: Pinocembrin enhanced flap survival, promoted neovascularization, mitigated oxidative stress, and suppressed pyroptosis and inflammation by downregulating the TLR4/NF-κB/NLRP3 signaling pathway.