Soluble fractalkine has a distinctive role of inflammatory process in neuronal system, however, it have not been investigated in Alzheimer's disease (AD). In the present study, we evaluated the plasma soluble fractalkine levels in patients with cognitive impairment and healthy control subjects and investigated the alterations of plasma soluble fractalkine levels within the patient group. One hundred-two patients with cognitive impairment including 51 mild cognitive impairment (MCI) and 51 AD patients, and 57 healthy control subjects enrolled in this study. The Mini Mental Status Examination (MMSE) and Global Deterioration Scale (GDS) was used to evaluate the severity of cognitive impairment of the patients. Human plasma soluble fractalkine were measured by using specific enzyme-linked immunosorbent assay. The plasma soluble fractakline significantly increased in the patient group in comparison to the control group. Significant differences in plasma soluble fractalkine levels with a sequential decrease trend were found among the MCI, the mild to moderate AD, and severe AD patients Also, the MMSE scores had positive correlation between MMSE scores and plasma soluble fractalkine in the patient group. This study provides the evidence that the soluble fractalkine is likely to play some roles in AD pathogenesis. In addition, the soluble fractalkine may be a possible biomarker of AD onset and progression.