Increased platelet activity plays a key role in atherothrombotic events. Persistent platelet activity has been reported in patients with atrial fibrillation (AF) following myocardial infarction and in the chronic phase after ischemic stroke. However, platelet activity in patients with AF remains clear. This study investigated platelet reactivity (expressed by CD62p) in patients with chronic nonvalvular (NV) AF. Expression of CD62p was measured by flow cytometry in 62 consecutive patients with chronic NVAF (defined as sustained AF > 6 months) and no previous embolic events. The CD62p expression was also evaluated in 20 healthy subjects. Expression of CD62p was not different between AF patients and healthy subjects (P = 0.970). Additionally, CD62p expression did not differ between patients with and patients without the following atherosclerotic risk factors: hypertension, current smoking, and hypercholesterolemia (all P values > 0.1). Furthermore, CD62p expression did not differ between patients taking and not taking the following medications: warfarin, a statin, or an angiotensin converting enzyme inhibitor/angiotensin II receptor blocker (all P values > 0.2). However, diabetes mellitus (DM) was strongly associated with increased CD62p expression (P < 0.0001). Multiple linear regression analysis demonstrated that only DM independently predicted increased CD62p expression (r2 = 0.509, regression coefficient = 3.044, P < 0.0001). In conclusion, compared to healthy subjects, CD62p expression was not significantly enhanced in chronic NVAF patients. However, CD62p expression was substantially elevated in diabetic patients with chronic NVAF.