Introduction: The SDF-1/CXCR4 axis is important in the recruitment of stem cells to the sites of injury. Some organs respond to damage by increasing expression of SDF-1/CXCR4. However, the possible role of this axis in skin wound healing specially in the case of Hair Follicle Stem Cell (HFSCs) applied wounds has received low attention to date. Methods and Materials: Animals (male rats) were divided into three groups: 1) Control (non-treated), 2) Vehicle (PBS) and 3) HFSCs (treated with Hair Follicle Stem Cells). The Bulge region of rat whiskers was isolated and cultured in DMEM/F12, then transplanted to wound site. At the end of the treatment period, in three different days (3, 7 and 14), Morphological and histological assessments, and molecular assays (ELISA and RT-PCR) for VEGF, SDF-1a and CXCR4 were performed. Results: Morphological analysis of wounds exhibited early wound closure in HFSCs group. In histological analysis, the diameter of epidermis, Amount of collagen formation and wound healing percent in HFSCs group were significant compared with control group (P<0.05). in molecular assays, angiogenesis (VEGF level), SDF-1a and CXCR4 expression and protein secretion in HFSCs groups were more significant compare with control group (P<0.05). Conclusion: Transplantation of HFSCs, induce secretion of SDF-1 and CXCR4 expression in wound bed which play important role in angiogenesis and accelerate cutaneous wound healing.