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Multiple studies have demonstrated that mechanical forces promote the growth of adipose tissue. However, the mechanism of adipose tissue regeneration induced by mechanical forces remains unclear.In an experiment using rats, prefabricated adipose tissue with a vessel pedicle was expanded using an external volume expansion device. The volume of fat flaps was tested at different time points. Cell proliferation and angiogenesis were analyzed using immunofluorescence. The expression of adipogenic genes and inflammatory cytokines was evaluated using real-time polymerase chain reaction analysis and enzyme-linked immunosorbent assay, respectively.There were more CD31+ cells and Ki67/CD34+ cells in the experimental group than in the control group. The number of Ki67/CD34+ cells peaked at 1 to 4 weeks. However, the expression levels of peroxisome proliferator-activated receptor-γ and CCAAT/enhancer-binding protein-β were highest from 4 to 12 weeks in the experimental group. Compared with the control group, the experimental group showed more proinflammatory cytokines: interleukin-1β, interleukin-6, tumor necrosis factor-α, and macrophage migration inhibitory factor.The construction of expanded prefabricated adipose tissue by mechanical forces is a dynamic and complex process. Mechanical forces promoted cell proliferation and angiogenesis in the early stage of adipose tissue regeneration (before 4 weeks) and induced adipogenic differentiation at a later stage (after 4 weeks) through up-regulation of macrophage migration inhibitory factor, which provided an adipogenic inductive microenvironment.