Objective. Currently, autologous fat transplantation (AFT) still has a low graft survival rate. Elevation of the AFT graft survival rate is a challenge. This study investigated the effect of hyperbaric oxygen (HBO) on AFT. Methods. Twelve adult male SD rats were randomly divided into two groups after AFT: the control group ( n = 6 ) and the HBO group ( n = 6 ). The rats were killed at 7, 14, and 28 days after transplantation to take the transplanted adipose tissues. The volume and weight of the tissues were detected. The pathological changes in the adipose tissues were observed after H&E staining. Microvessel density and levels of transforming growth factor- (TGF-) β, tumor necrosis factor- (TNF-) α, and malondialdehyde (MDA) in the transplanted adipose tissues were measured with CD31 immunohistochemical stain, ELISA, and biochemical reagents, respectively. Additionally, the protein expression levels of vascular endothelial growth factor- (VEGF-) A and platelet-derived growth factor- (PDGF) A in the adipose tissues were detected by Western blot. Results. HBO significantly preserved the volume and weight of the transplanted adipose tissue ( p < 0.01 ) and maintained the pathological structure of the transplanted adipose tissue. HBO therapy was effective in reducing inflammatory factor (TGF-β and TNF-α) levels and oxidative stress (MDA) in the transplanted adipose tissue ( p < 0.01 ) and significantly increased the level of CD31 and angiogenesis-related factors including VEGF-A and PDGF-A ( p < 0.01 ) to promote angiogenesis. Conclusion. HBO therapy regulated the immune response of fat grafts, stimulated their angiogenesis, and ultimately promoted their survival after AFT.