Background: Chronic kidney disease is a global public health problem that shortens lifespan by increasing the risk of cardiovascular disease. Aim: This study aimed to investigate the cardioprotective effect of erythropiotein (EPO) on uremic cardiomyopathy (UCM) and targeting the possible role of NFκβ. Methods: UCM was induced surgically in rats via a one-step 5/6th nephrectomy procedure. Serum level of Urea and Creatinine were measured to assess renal function. Also, EF%, FS% , LVDd & LVSd were estimated to assess the cardiac function . Moreover, tissue level of NFκβ, IL1 , IL6 and TNFα were measured to assess the possible mechanism .Results: UCM caused a significant increase in urea , creatinine , IL1 , IL6 , TNFα ,NFκβ , LVDd & LVSd with a significant decrease in EF% & FS%. Administration of EPO caused a significant improvement of the aforementioned UCM effects. Conclusion, EPO has cardioprotective effect in UCM targeting NFκβ.