Autogenous microfat grafting is widely used to augment depressed deformities or for other cosmetic purposes. Since the microfat survival rate is unpredictable due to absorption and calcification, previously cryopreserved fat is widely used for secondary procedures. Sphingosylphosphorylcholine (SPC) is a lysophospholipid, which has a role in several cellular responses, and is known to stimulate DNA synthesis and proliferation. Since endothelial progenitor cells (EPCs) are known to enhance the survival rate of transplanted fat tissue, the present study assessed the effects of SPC on EPCs, in order to verify its positive effects on proliferation. Cryopreserved human fat tissues mixed with various concentrations of SPC were grafted into the nude mouse model. After grafting, the viability of each SPC mixed group was determined and compared with that of the non‑SPC group. SPC exhibited a positive effect on EPC proliferation and angiogenic potential over 3 days when used at specific concentrations. The fat grafts of the 3 µM SPC‑treated group weighed significantly more and the volume was markedly increased, as compared with the control group. A reverse transcription‑quantitative polymerase chain reaction was conducted on the total RNA extracted from SPC‑treated fat tissues, which detected increased mRNA expression levels of matrix metallopeptidase‑9 and tumor necrosis factor‑α compared with in the control group. These results indicate that specific concentrations of SPC may exert favorable effects on grafted cryopreserved human fat tissue, which may be due to the increased mRNA expression levels of genes associated with angiogenesis.