Mueller matrix polarimetry is a potentially powerful technique for obtaining microstructural information of biomedical specimens. Thus, it has found increasing application in both backscattering imaging of bulk tissue samples and transmission microscopic imaging of thin tissue slices. Recently, we proposed a technique to transform the 4 × 4 Mueller matrix elements into a group of parameters, which have explicit associations with specific microstructural features of samples. In this paper, we thoroughly analyze the relationships between the Mueller matrix transformation parameters and the characteristic microstructures of tissues by using experimental phantoms and Monte Carlo simulations based on different tissue mimicking models. We also adopt quantitative evaluation indicators to compare the Mueller matrix transformation parameters with the Mueller matrix polar decomposition parameters. The preliminary imaging results of bulk porcine colon tissues and thin human pathological tissue slices demonstrate the potential of Mueller matrix transformation parameters as biomedical diagnostic indicators. Also, this study provides quantitative criteria for parameter selection in biomedical Mueller matrix imaging.