Parkinson's disease (PD) is the second most common progressive neurodegenerative disorder and is characterized by loss of dopaminergic neurons. Biomarkers for tracking disease progression are useful indicators of the pathological conditions or the effects of therapeutic interventions on disease progression, but there are currently no known biomarkers in the blood that correlate with the progression of PD. Several studies have suggested that exosomes reflect intracellular changes that occur in response to pathological conditions and are an effective source of biomarkers for disease progression. To identify candidate biomarkers of disease progression in PD, we isolated exosomes from plasma of PD patients at Hoehn and Yahr (HY) stages II and III and performed protein profiling of the exosomes using two-dimensional differential gel electrophoresis (2D-DIGE). The expression levels of three proteins (clusterin, complement C1r subcomponent, and apolipoprotein A1) in PD patients at HY stages II and III were significantly decreased compared to healthy subjects (p < 0.05). Apolipoprotein A1 in PD patients at HY stage III was significantly decreased compared to HY stage II and correlated with progression of PD (r < -0.77, p < 0.01). Fibrinogen gamma chain in plasma was also decreased in PD patients at HY stages II and III compared to healthy subjects. Therefore, these three exosomal proteins (clusterin, complement C1r subcomponent, and apolipoprotein A1) and fibrinogen gamma chain in plasma may be biomarker candidates for the diagnosis of PD. In particular, the expression levels of apolipoprotein A1 in exosomes may be useful for tracking the progression of PD.