BACKGROUND AND PURPOSE: Inflammation is closely related to the pathogenesis of multiple system atrophy (MSA). As markers of inflammation, the monocyte to high-density lipoprotein ratio (MHR), neutrophil to lymphocyte ratio (NLR), and red cell distribution width to platelet ratio (RPR) have been proven to be associated with a large variety of diseases. The aim of this study was to explore the association between inflammatory markers (MHR, NLR, and RPR) and MSA, and the difference between MSA and Parkinson's disease (PD) was further compared by these inflammatory markers. MATERIALS AND METHODS: This study was divided into three groups: 47 patients with MSA, 125 patients with PD, and 124 healthy controls. The corresponding laboratory indicators of subjects were collected and analyzed to obtain MHR, NLR, and RPR values. RESULTS: Compared with healthy controls, the MHR, NLR, and RPR were higher in the MSA group ( < 0.05), and the MHR was higher in the MSA group than in the PD group ( < 0.001). Multivariate logistic regression analysis showed that MHR10 (corrected OR = 1.312, 95% CI 1.093-1.575) and RPR100 (corrected OR = 1.262, 95% CI 1.055-1.509) were positively correlated with the risk of MSA. The receiver operating characteristic (ROC) curve indicated that the areas under the curve (AUCs) of the MHR, NLR, and RPR for predicting MSA were 0.651 (95% CI 0.562-0.74; < 0.05), 0.6 (95% CI 0.501-0.699; < 0.05), and 0.612 (95% CI 0.516-0.708; < 0.05), respectively. The AUC of MSA and PD predicted by the MHR was 0.727 ( < 0.001). When the cut-off value was 0.38, the sensitivity and specificity were 60 and 77%, respectively. Spearman correlation analysis showed that the MHR was significantly and positively correlated with the course of MSA cerebellar type (MSA-C) patients. CONCLUSION: There may be peripheral inflammation in patients with MSA. Compared with NLR and RPR, MHR has higher predictive value for the diagnosis and differential diagnosis of MSA.