The hormone melatonin, secreted from the pineal gland at night and suppressed during the day, provides a circadian and seasonal signal to the organism. The impact of pharmacological doses of melatonin on erythrocyte deformability was investigated by our group in several studies in both in vitro and in vivo conditions. The aim of this study was to investigate the effects of alterations in the physiological melatonin levels via the circadian rhythm on erythrocyte deformability. 50 male rats weighing 250-300 g were divided in 5 groups. The rats were subjected to 12/12, 24/0, 0/24, 16/8 and 8/16 h of Light/Dark (L/D) cycle, respectively. The elongation indexes (EI) of the erythrocytes were measured by a laser diffractometer (Myrenne Rheodyne SSD) by using 30 microl of whole blood suspended in 2 ml of Dextran 60. There was no significant difference in the EI of the 24/0 h L/D group compared to the control (12/12), whereas the decrease of EI was statistically important in the 0/24 h L/D group (p = 0.009). This decrease in EI was also significant when this group was compared to the 24/0 h L/D group (p = 0.05). Furthermore, the EI was affected significantly by alterations in the circadian rhythm, compared to control (16/8, 8/16 h L/D; p = 0.05 and p = 0.007, respectively). As a result, the alterations in physiological melatonin levels via different circadian rhythms have significant impacts on the deformability of erythrocytes, which therefore may cause important cardiovascular implications in the people who are exposed to different light dark cycles. Furthermore, these data represents a new and a quite crucial open-field to be investigated and taken into account in in vivo hemorheological studies.