Upon lipopolysaccharide (LPS) stimulation, phosphoinositide 3-kinase (PI3K)/Akt pathways serves to banlance proinflammatory and anti-inflammatory responses.However, the mechanism underlying Akt signaling mediated process is not well understood.The aim of this study was to investigate the effect of inhibition of Akt in the septic murine model.Adult male Sprague-Dawley mice were injected with lipopolysaccharide (LPS, 4 mg/kg, i.p.) to induce sepsis.Next, the levels of p-Akt, Mitogen-activated protein kinases (MAPKs) including ERK1/2, p38 and ERK5, as well as cytokines were detected.In the septic mice, when the Akt inhibitor AZD5363 was injected (10 mg/kg) 4 h prior to the administration of LPS, the LPS injection induced an increased Akt phophorylation in the heart.Addition of AZD5363 significantly increased the levels of ERK1/2, p38, GSK3β, and PKCα,as well as the levels of TGF1 and FGF2, compared with in the rats following solely LPS injection.In addition, the VEGF and COX2 levels were markedly decreased in the rats administrated with AZD5363.Taken together, inhibition of Akt signaling pathway augments septic symptoms via MAPK signaling pathway activations and increased levels of cytokines.