Introduction Partial ligation of portal branches leads to atrophy of the deprived lobes and hypertrophy of the intact lobes. The trigger of the liver regeneration cascade is currently not completely known. It is hypothesized that an increased shear stress in the hepatic circulation due to higher portal blood flow velocity causes release of NO and thus triggers liver regeneration. For the first time this in vivo study examines the effects of portal branch ligation on liver microcirculation. Methods Under isoflurane gas anaesthesia the left portal branch was ligated (PBL) in male Sprague-Dawley rats. At day 1 and 3 after PBL (n=5 per group) fluorescence microscopic analysis of the hepatic microcirculation of the ligated and non-ligated lobes was performed. One group without PBL served as control (C,n=4). Sinusoidal flow velocity was assessed by fluorescence tagged latex beads. Additional measurements included sinusoidal perfusion rate and diameter as well as leukocyte-endothelium interaction. Sinusoidal blood flow and shear stress were calculated. Mean±SEM, unpaired t-test; *p<0.05 vs. C. Results At day 1 in PBL areas sinusoidal flow velocity was reduced compared with controls (μm/s;1d-PBL267±8* vs. C313±16), whereas flow velocity in non-ligated lobes (NLL) was markedly elevated (μm/s;1d-NLL554±70*). At day 3 flow velocity remained elevated in NLL and reduced in PBL (μm/s;3d-PBL242±14*, 3d-NLL523±75*). Sinusoidal diameters were significantly reduced in the NLL group versus both the control and the PBL group at day 1 and 3 (μm;1d-NLL 6,5±0,3*, 3d-NLL6,5±0,2* vs. C7,9±0,4; 1d-PBL 9,3±0,5, 3d-PBL 9,1±0,3), whereas sinusoidal diameters in the PBL group were only slightly increased. In NLL groups, shear stress was markedly higher at day 1 and 3 compared to controls and the PBL group (dynes*cm-2;1d-NLL 13,4±1,8*, 3d-NLL 12,8±2* vs. C 6,4±0,3), whereas shear stress in the PBL group was reduced (dynes*cm-2;1d-PBL4,5±0,4*, 3d-PBL4,3±0,3* vs. C6,4±0,3). Sinusoidal blood flow showed no significant difference and remained stable at day 1 and 3, but sinusoidal perfusion rate after PBL was reduced at day 1 and 3 (%;1d-PBL 93±4*, 3d-PBL 88±6* vs. C100±0). Discussion This in vivo study demonstrates an elevation of shear stress in NLL together with a reduction in PBL lobes at different time points after left portal branch ligation, whereas sinusoidal flow was kept constant in all areas. This underlines the hypothesis that shear stress plays a pivotal role to trigger liver hypertrophy in the NLL. In addition, the study clearly shows that the organ liver aims at a constant tissue mass and sinusoidal blood flow, most probably in favour of maintenance of clearance function.