Culture broths from Phanerochaete chrysosporium and Trametes cingulata, combined with co-factors such as hydrogen peroxide, dithiothreitol, copper, iron, and manganese ions were examined for the ability to modify lignin structure. High-performance size exclusion chromatography (HP-SEC) coupled to multi-angle laser light scattering (MALLS) detection was used to determine the effect of several white rot fungi, pH values, enzymes, and co-factors on the molecular weight distribution of treated kraft lignin. The analytical procedure tracked changes in molecular weight distribution, radius of gyration, and hydrodynamic radius. Results showed changes in the molecular weight distribution of lignin components when treated with combinations of factors. The induced cultures showed more lignin depolymerization for the specific lignin samples in which they were initially grown. The distribution in the radius of gyration became narrower with time, indicating that molecular conformation changed to a more uniform molecular shape. H2O2 and DTT showed the most significant changes in lignin molecular weight distribution.