Sepsis is one of the most serious problems of modern medicine nowadays and improvements in treatments are urgently needed. Bone marrow derived stromal cells (BMSCs) have a potent immunosuppressive effect in humans in vivo. IL-10, a cytokine synthesis inhibitory factor, plays an important role in anti-inflammatory response. Here BMSCs were infected with recombinant adenovirus encoding murine IL-10 (mIL-10) and a GFP marker to obtain GFP positive BMSC-mIL-10 cells. The BMSC-mIL-10 cells were injected into mice with cecal ligation and puncture (CLP)-induced sepsis, and the enhanced expression of IL-10 in blood was confirmed by ELISA. Indeed, in CLP mice mode, the systematic delivery of IL-10 via BMSCs effectively suppressed the production of proinflammatory cytokines, including TNF-α, IL-6, IL-1α and IL-1β, compared to BMSCs alone. The therapeutic benefits were further demonstrated by an increased prevention from body loss, increased survival rate, and the suppression of inflammatory response in lung and kidney. Furthermore, these effects may be mediated by inhibiting the activation of NF-κB in macrophages and neutrophils. Collectively, these results suggest that systemic delivery of IL-10 by BMSCs may serve as a potential treatment in sepsis therapy.