<p>Objective. To investigate the clinical relationship between the interaction of iron metabolism, neuroinflammation and iron deposition in substantia nigra of Parkinson’s disease (PD). Methods. 1) 30 PD patients and 30 healthy controls were recruited from the First and Second affiliated Hospitals of Xinjiang Medical University from May 2022 to October 2023. The clinical symptoms (motor symptoms and non-motor symptoms) and clinical severity of PD patients were evaluated by unified Parkinson’s disease scale III (UPDRSIII), Hoehn-Yahr (H-Y) stage, Hamilton anxiety scale (HAMA), Hamilton depression scale (HAMD), mini-mental state assessment scale (MMSE) and Montreal cognitive assessment scale (MoCA). (2) A case-control study was conducted to determine the content of iron in the brain of patients with PD by magnetic sensitive quantitative imaging (QSM) to generate 3DT2, 3DT2* (SWAN), QSM and PostT1Gd, and to study the correlation between iron content and motor symptoms, non-motor symptoms (anxiety, depression, dementia), and clinical severity in PD. (3) Enzyme-linked Immunosorbent Assay (ELISA) was used to detect and compare the levels of iron, DMT1, FPN1, IL-1β, IL-6 and TNF-α in the peripheral blood of both groups, and t-test and Wilcoxon rank-sum test were used to analyze the correlation between peripheral iron metabolism and blood inflammatory factors, clinical symptoms and clinical severity in patients with PD. (4) To analyze the clinical correlation between the interaction of peripheral iron metabolism and neuroinflammation and iron deposition in substantia nigra of Parkinson’s brain. Results. 1) The quantitative susceptibility mapping (QSM) values of red nucleus, substantia nigra, putamen and caudate nucleus in PD group were higher than those in control group (P &lt; 0.05). The QSM value of red nucleus in PD group was negatively correlated with UPDRSIII score (motor symptoms) and positively correlated with non-motor symptoms depression (P &lt; 0.05). The QSM score of substantia nigra in midbrain was positively correlated with disease severity (H-Y stage)(P &lt; 0.05). (2) The median levels of serum DMT1, Fe, IL-6 and TNF-α in PD group were higher than those in control group (P &lt; 0.05). The median level of serum FPN1 in PD group was lower than that in control group (P &lt; 0.001). There was a negative correlation between serum DMT1 and non-motor symptom intelligence (MMSE), and between peripheral blood iron content and anxiety in patients with PD (P &lt; 0.05). There was no significant correlation between ferritin and inflammatory factors and other clinical symptoms and severity of PD (P &gt; 0.05). (3) The quantitative value of magnetic sensitivity (QSM) of substantia nigra in PD was positively correlated with iron metabolic protein DMT1, peripheral blood inflammatory factor IL-6 and negatively correlated with peripheral blood iron ion (P &lt; 0.05). The results of interactive analysis showed that there was interaction among magnetic sensitivity quantitative value of substantia nigra (QSM), iron metabolic protein DMT1, peripheral blood inflammatory factor IL-6 and peripheral blood iron ion. Conclusion. There are iron deposits in the deep nuclei and thalamus of PD patients. Iron deposition in substantia nigra is related to UPDRSIII score (motor symptoms) and disease severity (H-Y stage) in patients with PD. Iron deposition in substantia nigra may be linked to the interaction between iron metabolism and neuroinflammation.</p>