Inflammation is one of the body¡¯s natural responses to injury and illness as part of the healing process. However, persistent inflammation can lead to chronic inflammatory diseases or multi-organ failure. Altered mitochondrial function has been implicated in several acute and chronic inflammatory diseases through induction of an abnormal inflammatory response. Therefore, treating inflammatory diseases through recovery of mitochondrial function may be a potential therapeutic approach. Recently, mitochondrial transplantation proved beneficial in hyperinflammatory animal models. However, it is unclear how mitochondrial transplantation attenuates inflammatory responses induced by external stimuli. Here, we isolated mitochondria from umbilical cord-derived mesenchymal stem cells, referred as to a PN-101. We demonstrated that PN-101 significantly reduced LPS-induced mortality in mice. In addition, in phorbol 12-myristate 13-acetate (PMA)-treated THP-1 macrophages, PN-101 attenuated the LPS-induced increase production of pro-inflammatory cytokines. Furthermore, we showed that anti-inflammatory effect of PN-101 is mediated by blockade of the phosphorylation, nuclear translocation, and trans-activity of NF¥êB. Taken together, our results demonstrate the therapeutic potential to attenuate pathological inflammatory responses using PN-101.