Background: High potassium diets have been shown to be beneficial in cardiovascular disease partly because of blood pressure lowering effect. The effect of potassium on inflammation has not been studied. We investigated the influence of potassium supplementation on the degree of renal inflammation and the intracellular signaling mechanisms that could mediate inflammation in chronic kidney disease (CKD). Method: CKD was created in male Sprague-Dawley rats by subtotal nephrectomy. Two groups of CKD rats were pair fed with diets containing 2.1% potassium (potassium supplemented diet) or 0.4% potassium (basal diet). Body weight, blood pressure, blood and urine electrolytes were measured biweekly. The animals were euthanized at week 8, and the remnant kidneys were analyzed by histology, immunohistochemistry, Western-blot, and real-time quantitative PCR. Results: In the CKD pair-fed groups, blood potassium concentration did not differ significantly, but blood pressure was lower in the potassium supplemented group. Compared to the basal diet, potassium supplementation decreased renal tubulo-interstitial injury and suppressed renal inflammation as evidenced by decreased macrophage infiltration, lower expression of inflamematory cytokines and decreased NF.B activation. These renoprotective effects were associated with downregulation of renal TGF, upregulation of renal Smad7 and lower blood pressure. Conclusion: Our results show that potassium supplementation can reduce renal inflammation and hence, could modulate the progression of kidney injury in CKD.