Chronic renal diseases with enhanced glomerular protein filtration are accompanied by tubulointerstitial inflammation and progression to renal function deterioration. Filtered protein, like albumin, is a pathogenic factor per se in the progression of renal diseases. The nuclear factor κB (NF-κB), a ubiquitous transcription factor, mediates the expression of numerous inflammatory or fibrotic mediators such as RANTES, MCP-1, TNF-α, cytokine receptors, or iNOS in renal as well as in other tissues. It is evident that NF-κB is involved in protein-overload stimulated renal inflammatory mechanisms. This paper reviews the recent studies concerning NF-κB-activation and expression inducing renal inflammation and fibrosis in several proteinuric animal experimental models as well as protein-induced NF-κBmediated renal inflammatory signal transduction pathways in vitro, with a special focus on albumin-endocytosis in proximal tubular cells. Protein-induced NF-κB-activation and NF-κB-mediated signal transduction pathways seem to be interesting therapeutic targets in proteinuric renal diseases. Therefore, this paper shows recent pharmaceutical approaches to inhibit renal NF-κB-activity.