The pathogenesis of type III MPGN appears similar to that of type I MPGN. Indeed, many consider type III MPGN to be a morphologic variant of type I, although the pathogenetic mechanisms underlying the differences seen on electron microscopy remain poorly understood.

In all MPGN types, complement activation drives injury to the glomerular capillaries and mesangium. Inflammatory cells, especially monocytes, may be recruited to various degrees and contribute to the damage. Following inflammation, reactive processes of cellular proliferation and repair cause mesangial matrix expansion, as well as duplication of the glomerular basement membrane. By disrupting the normal components of the filtration barrier, these inflammatory processes result in hematuria and proteinuria.