Apoptosis of implanted mesenchymal stem cells (MSCs) limits the efficiency of MSC therapy. Recent studies showed the ligands of Toll-like receptors (TLRs) could control the function of these cells. We have investigated the effect of lipopolysaccharides (LPS), a ligand of TLR4, on the survival of MSCs and explored the roles of TLR4 and PI3K/Akt. H(2)O(2)/serum deprivation(H(2)O(2)/SD) induced apoptosis of MSCs but LPS-preconditioning (1.0microg/ml) protected MSCs from H(2)O(2)/SD-induced apoptosis and promoted their proliferation. Western blotting showed that 1.0microg/ml LPS enhanced phosphorylation of both Akt at Ser 473 and nuclear factor-kappa B (NF-kappaB) p65 at Ser 536. However, the protective effects of LPS on survival were not observed in TLR4(lps-del) MSCs. The results suggest appropriate treatments with LPS can protect MSCs from oxidative stress-induced apoptosis and improve the survival of MSCs via the TLR4 and PI3K/Akt pathway.