Background and Aim: Neuroinflammation plays an early and prominent role in the pathology of Parkinson disease. Tumor necrosis factor alpha induced protein-8 like-2 (TIPE2) is a relatively new subtype of tumor necrosis factor which may play a role in pathogenesis of Parkinson disease. Our aim was to evaluate the role of serum level of TIPE2 as a risk factor for Parkinson disease and as a serological biomarker of disease severity. Methods: Forty-seven patients diagnosed as idiopathic PD according to diagnostic criteria of the UK Parkinson Disease Society Brain Bank, and 47 healthy individuals were enrolled. All patients were on medical  treatment of PD and were evaluated by Unified Parkinson's disease Rating Scale (UPDRS), and Modified Hoehn and Yahr staging scale(HY). Cognitive function was assessed using Montreal Cognitive Assessment Scale (MOCA). TIPE2 serum level was measured in all participants. Results: PD patients had significantly higher levels of TIPE2 (P-value <0.001). Also, PD patients with cognitive impairment had significantly higher levels of TIPE2 (P-value= 0.039). TIPE2 level was positively correlated with score of modified HY staging (p-value o.oo1). Also,TIPE2 level was positively correlated with bradykinesia, total motor sub scores of UPDRS and total score of UPDRS (p-value 0.009, 0.019, 0.027 respectively). There was a significant negative correlation between TIPE2 and the scores of executives and visuospatial functions, attention, abstraction and total score of MoCA. Conclusions: TIPE2 serum levels in PD patients are higher than its serum level in healthy controls. Such high level of TIPE2 has a considerable impact on disease severity.