Recently, mesenchymal stem cells-derived microvesicles (MMVs) attract much attention as a strategy of cell-free treatment. In our study, we found that MMVs could improve the organ dysfunction during sepsis. To investigate the mechanism, we harvested MMVs from mesenchymal stem cells to perform proteomic analysis, and chondrocyte-derived microvesicles (CMVs) were used as a negative control, and PGC-1α overexpressed-MMVs were used as a positive control. A total of 5411 proteins were identified in this study, and differentially expressed (DE) proteins were further identified with a cut-off of absolute fold change >1.5 and a significance p-value <0.05. Compared with CMV group, 321 proteins were upregulated and 209 proteins were downregulated in MMVs. This study illustrated the differences between MMVs and CMVs, and provided a sight for investigating the protective effect of MMVs.