Arterio-venous fistula (AVF) is the first option for hemodialysis. This study evaluated the carotid-jugular-fistula (CJF) as a model to study fistula-related microcirculatory and systemic changes and presented the hemorheological changes as a suggested mechanism of the impaired tissue perfusion. Sixteen female Wistar rats were used in this study, ten in fistula-group (FG) and six in sham-operated-group (SG). Carotid-Jugular-Anastomosis was done in FG, while the same vessels were just isolated in SG. The rats were followed-up for 6 weeks. Hematological and hemorheological parameters were measured before the operation, and on 1st and 6th postoperative weeks. Besides hemodynamic parameters, the liver and kidney microcirculation were evaluated using laser Doppler device at the 6th week measurements, and the effects of fistula occlusion on the microcirculation were evaluated as well. The animals in FG group showed significant decrease in hemodynamic parameters after the fistula. Liver microcirculatory blood flux units (BFU) were significantly lower in FG in comparison with SG and increased significantly after the occlusion of the fistula. Kidney BFU showed closer changes but without significant differences. Erythrocyte deformability significantly impaired in FG after the fistula. Morphologically marked increase in absolute and relative heart weight values was found with left ventricular hypertrophy. The carotid-jugular fistula acted as a feasible model of AVF. Besides the well-known hemodynamic effects, the presence of the CJF resulted in impaired Erythrocyte deformability and mechanical stability. These changes could be one of the pathways through which the arteriovenous fistula may influence the microcirculation.