Background The pathophysiological mechanism of hypertensive retinopathy (HR) is not fully understood, although it is thought that increased platelet activation may have a pivotal role. This study was designed to investigate this possibility by determining the frequency and magnitude of mean platelet volume (MPV), a marker of platelet activation, in HR. Methods One hundred and thirty-eight patients, aged 31 to 80 years, who had essential hypertension with HR were enrolled in the study. The patients who presented at the emergency and outpatient medical department of the Capital Development Authority (CDA) Hospital, Islamabad, Pakistan, from March 2013 to February 2014 were selected for this study. All patients were analyzed for grading of HR according to the Keith-Wagener-Barker (KWB) classification criteria. A direct ophthalmoscopic examination was performed in all the subjects, together with an assessment of MPV. Results The mean age of the patients was 54.1 ± 11.7 years. Normal MPV was found in 97 (70.2%) patients, 53 males and 44 females. Elevated levels of MPV were found in 41 (29.7%)  patients, 19 males and 22 females. In patients with Grade 1 HR, the MPV was 10.6 ± 0.6 femtoliters (fl). In Grades 2, 3, and 4 HR, the values of MPV were 11.1± 0.5 fl, 11.6 ± 0.3 fl, and 12.2 ± 0.6 fl, respectively, which were greater than the normal range (> 10 fl) of MPV values. In addition, the frequency of elevated MPV significantly (P < 0.001) and linearly (r = 0.998) increased with increasing HR grade. Conclusion It is concluded that the frequency of elevated MPV is increased in patients with HR and strongly correlates to grade. In addition, the magnitude of the elevated MPV increased with the severity of the retinopathy. Thus, abnormally elevated MPV may be an etiological factor for HR in hypertensive patients.