Transplantation of human umbilical cord mesenchymal stem cells (UC-MSCs) has been shown to be effective in treating critical limb ischemia (CLI). However, the mechanism of MSCs- mediated improvements in CLI patients, especially with respect to the immune- inflammatory aspects of this disease, is still unknown. In this study, we investigated the changes in T-lymphocyte subpopulations and inflammatory mediators (such as IL-6, IL-10 and TNF-α) in PBMCs from CLI patients after UC-MSCs treatment, as well as the correlation between inflammatory mediators and EPCs. TNF-α serum levels increased at 24 h (p=0.017) after treatment and then decreased at 1 month (p=0.031) compared with that before treatment. IL6 serum levels increased at 24 h (p=0.099) after treatment and then decreased at 1 month (p=0.072) compared with that before treatment. The percentages of CD3+ T, CD3+ CD4+ lymphocytes and NK cells were significantly decreased after UC-MSCs treatment (p=0.002, p=0.012 and p=0.029, respectively). TNF-α (r=-0.42, p=0.0004) and IL-6(r=-0.33, P < 0.0001) were shown to be inversely correlated with the number of circulating EPCs. Our studies have shown that UC-MSCs have anti-inflammatory and immunomodulation properties in CLI and promotes healing of non-healing wounds.