Hyperechogenicity of the substantia nigra (SN) is a sensitive marker for Parkinson's disease (PD). Previously, a relation between SN echogenicity and iron as well as neuromelanin content could be described in 60 human brains. In the present study on a subset of 33 brains, SN echogenicity was found to be correlated with microglia activation (ρ = 0.46, p = 0.008) after correction for iron and neuromelanin content. These findings strengthen the hypothesis of a close pathophysiological connection between SN hyperechogenicity and PD pathology.