Abstract: Objective To study the role of WYE-354,an ATP-competitive mammalian target of rapamycin（mTOR） kinase inhibitor,in anti-rejection of mice after skin allograft and its mechanism. Methods A skin allograft model was established with BALB/c mice as the donor and C57BL/6 mice as the recipient.The mice were divided into auto-graft group（control group） and allograft group（WYE-354 group）.Mice in control group were given rapamycin and WYE-354 2 days after operation for 2 days and those in WYE-354 group received oral 0.2ml rapamycin（1mg/kg·d） and injection of WYE-354 at dose of 1mg/（kg·d）,1.5mg/（kg·d） and 50mg/（kg·d）,respectively.On days 3,7,11,and 21 after operation,4E-BP1 phosphorylation levels in spleen cells were measured by Western blot.On day 11 after operation,skin tissue sample was stained with H＆E. Results The survival time of mice in WYE-354 group was longer than that of mice in control group（P＜0.01）.The survival time of mice in control group was longer than that of mice in medium and high dose WYE-354 groups（P＜0.01）.The number of locally-infiltrated lymphocytes was less in low dose WYE-354 group than in control group.The 4E-BP1 phosphorylation level in spleen cells was down-regulated in control group and low,medium and high WYE-354 groups,especially in high dose WYE-354 group. Conclusion WYE-354 can inhibit the 4E-BP1 phosphorylation level related with the mTOR signal transduction pathway,block the cell cycle,reduce the infiltration of lymphocytes to skin grafts,and prolong the survival time of mice after skin graft.