Abstract: Objective To investigate the effects and mechanisms of a novel recombinant fusion protein,TNFR2-FcIL-1ra（TFI）on cardiac hypertrophy. Methods Twenty-four male 8-week C57BL/6Jhealthy mice were randomly divided into threee groups:control group（NS）,model group angiotensinⅡ（Ang Ⅱ）,1500ng/（kg·min）,infused 7dand treatment groupAngⅡ1500ng/（kg·min）+TFI 5mg/（kg·2d）,8mice per group. On the7th day,blood pressure was measured by tail-cuff plethymography method,and cardiac structure and function were evaluated by small animal ultrasound. Mice treated with saline,AngⅡor combination of AngⅡand TFI were executed and processed immediately for morphological and gene expression analysis. Then hematoxylin-eosin（HE）and wheat germ agglutinin（WGA）staining were used to detect the cardiac morphological changes and myocyte size.In addition,the inflammatory markerstumor necrosis factorα（TNF-α）and interleukin 1β（IL-1β）of heart were assayed through immunohistochemistry. The mRNA levels of TNF-α,IL-1βand hypertrophic markersatrium natriuretic peptide（ANP）,β-myosin heavy chain（β-MHC）were tested by real-time quantitative PCR. Results Compared with the control group,blood pressure was significantly increased on the 1,3and 7th day,the left ventricular wall thicken at diastole and end-systole,cross section area of myocardial cells raised obviously （322.2±11.6）vs（199.7±12.4）μm2,the positive area of TNF-α（1.33±0.26）% vs（0.03±0.01）%and IL-1β（1.84±0.33）% vs（0.08±0.03）%increased,and mRNA level of TNF-α,IL-1β,ANP,andβ-MHC significantlyupregulated（all P＜0.05）in model group. Compared with the model group,there was no significant change in the blood pressure,but ventricular wall thickness eased;myocardium cell cross section reduced,the positive area of TNF-αand IL-1βlessened,and mRNA levels of TNF-α,IL-1β,ANP andβ-MHC decreased（all P＜0.05）in treatment group.Conclusions TFI could improve cardiac hypertrophy by inhibiting the inflammatory response.