Aim To study the effects of eplerenone （EPL） on heart failure and inflammatory cytokines in central nervous system. Methods Wistar rats were divided into sham group （n6）,PDTC treatment group （n10）,EPL treatment group （n10） and model group （n10）. Then these rats were administrated with PDTC （150 mg/（kg·d））,EPL （30 mg/（kg·d）） and clean distilled water. After six weeks,hemodynamic data was measured,then hypothalamus and serum samples were collected. Cytokines,nuclear factor kappa B （NF-κB）,corticotropin releasing hormone （CRH）,aldosterone （ALD） and norepinephrine （NE） was measured. Results Eplerenone and PDTC could improve heart function. In the model group,expression of ALD,NE,TNF-α,CRH,AngⅡ and NF-κB/p65 increased. Eplerenone and PDTC decreased the expression of these indexes effectively. Expression of CRH positive neurons in the hypothalamus of rats was significantly increased in the model group,which was decreased in eplerenone and PDTC treated group. Conclusions Eplerenone could improve heart function in rats with heart failure,which may be related to the inhibition of expression of inflammatory cytokines in hypothalamic paraventricular nucleus.