Parkinson’s disease (PD) is a chronic progressive neurodegenerative disorder characterised by selective loss of dopaminergic neurons in the substantia nigra. Drugs are the principal method of symptom treatment, yet remain unable to reverse underlying neurodegeneration. As PD prevalence increases with aging populations, greater emphasis falls on understanding pathogenesis to establish an effective neuroprotective strategy. Current research identifies iron accretion as a potential pathogenic factor. Iron is crucial for healthy cellular physiology, however, dysregulation can be highly neurotoxic. Since iron cannot be excreted, levels must be tightly controlled via specific iron regulatory proteins (IRP), including hepcidin, transferrin receptors, divalent metal transporter 1, ferritin, ferroportin, aconitase 1, and iron response element-binding protein 2. Iron accumulation has been established in neurodegenerative diseases, including Alzheimer’s, Multiple Sclerosis, and PD. While the instigating causes remain unknown, inflammation is a common factor. Activated microglia mediate the inflammatory response, and can release cytotoxic substances leading to iron-induced toxicity. Since dopaminergic neurons in PD are vulnerable to iron overload and inflammation, it is vital to determine what promotes changes to IRP expression leading to iron accumulation. It is hypothesised that chronic microglial activation and ensuing pro-inflammatory factors can dysregulate neuronal iron. Such changes may result from alterations in key IRP gene expression, with downstream cascades leading to neuronal degeneration. Results herein provide evidence of microglial inflammatory factor involvement on neuronal iron metabolism in an in vitro model of dopaminergic neurons. Specifically, IL6, TNF and new evidence of hydrogen peroxide instigate significant alterations in expression of HAMP, TfR and DMT1, causing iron elevations. Co-culture experiments established astrocytic iron buffering mechanisms able to provide sufficient neuroprotection to abolish observed gene expression changes. Lastly, experiments conclude that neuronal death occurs mainly via apoptotic pathways. Collectively, results support the instigative role of inflammation on altering neuronal iron handling. Such discoveries could lead to potential improvements in therapeutic strategies for PD.