The extracellular matrix, comprising the glomerular basement membrane and the mesangial matrix, plays a crucial role in glomerular structure and function. The glomerular extracellular matrix is composed of collagens, proteoglycans and glycoproteins. The distorted balance between synthesis and degradation of extracellular matrix proteins is a hallmark of many forms of glomerulonephritis, such as glomerulosclerosis. The degradation of the matrix occurs through the action of a group of extracellularly active metalloproteinases. Within the glomerulus these enzymes are synthesized by the epithelial and the mesangial cells. The molecular structure of the mesangial metalloproteinases, including their in vitro regulation, was analyzed and the in vivo synthesis of these proteinases was documented for cases of idiopathic rapid progressive glomerulonephritis and anti-Thy 1.1 nephritis. The therapeutic change in the activity and expression of the glomerular metalloproteinases, resulting in the restoration of physiologic matrix metabolic balance, opens up a new perspective for the therapy of glomerular inflammatory processes.