Parkinson’s disease (PD) is characterized by the degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Among other factors, microglia are thought to take part in the chronic neuroinflammatory scenario that contributes to the process of neuronal death. However, the factors that maintain the overreactive response of microglia in PD remain mysterious. As we wanted to simulate the chronic neuroinflammatory scenario taking place in PD, we evaluated the response of microglial cells after repetitive pro-inflammatory stimuli induced by LPS and IFN-g in vitro. In contrast with the over-reactivity of a single input, applying repetitive proinflammatory treatment to microglia reduced the release of nitrites, decreased their cell size, and most importantly impeded the effective phagocytic capacity when presented to dopaminergic cells in co-cultures, indicating the establishment of a tolerant or anergic state. Moreover, the characteristic translocation of NF-kB into the nucleus faded away. Taking this into account, we wanted to explore whether PD patients showed any trend of over-reactivity. We observed that phagocytic marker CD16 was significantly increased in PD patients suggesting a high reactivity of microglia and elevated phagocytic capacity. This phenotype relates with the activation state of microglia in contrast to the establishment of tolerance, suggesting that this phenomenon may be hampered in PD. Further exploration of evidence of deficient tolerance in parkinsonian microglia will allow to pinpoint their phenotypic state in this neurodegenerative disease.