Thymosin β 4 (T β 4) has been suggested to regulate multiple cell signal pathways and a variety of cellular functions such as cell migration, proliferation, survival and angiogenesis.Here,we investigated the effect of T β 4 on endothelial progenitor cells (EPCs) apoptosis induced by serum deprivation and the corresponding signal transduction pathways involved in this process.Incubation of EPCs with T β 4 caused a concentration dependent increase in cell viability and proliferation activity.It also caused an inhibitory effect on EPCs apoptosis, which was abolished by PI3K inhibitors (either LY294002 or Wortmannin) or JNK MAPK inhibitor SP600125.In addition, the expression and activity of caspase-3 and-9 were decreased by T β 4, which markedly increased Bcl-2 and Bc1-x1 protein expression with declined Bad and Bax.Furthermore, T β 4 was immunoprecipitated with integrin-linked kinase (ILK), accompanied by augmentation of ILK activity.Transfection of EPCs with ILK-siRNA resulted in abolishment of the activation of ILK-Akt and the ameliorative effect on apoptosis by T β 4.Together, T β 4 mediated inhibitory effect on EPCs apoptosis under serum deprivation can be attributed, at least in part, to ILK-Akt activation.The activation of JNK MAPK might also be involved in this process.