PURPOSE: The clinical advantages of end-to-end (ETE) anastomosis have not been clear despite its biomechanical advantage over end-to-side (ETS) anastomosis. We compared the histomorphometric features of intimal remodeling after ETE and ETS anastomosis in a rabbit aortic bypass model. METHODS: Thirty-two bypass operations, 16 with ETS and 16 with ETE anastomoses, were performed using aortic allografts of donor rabbits (15 per group) and polytetrafluoroethylene (PTFE) grafts (1 per group). To minimize bias from the immunologic response to aortic allografts or graft size, a long aortic tissue obtained from one donor was divided into 2 pieces and shared between each ETE and ETS bypass. PTFE graft bypasses, which are commonly used in clinical practice, were performed to provide comparison results for an allograft with a different compliance. Vessels were harvested at 1 day (1 per group), 5 days (1 per group), and 4 weeks (14 per group, including the PTFE bypass group) after surgery. Intimal thickening was evaluated with hematoxylin-eosin, van Gieson, immunohistochemical staining and Western blot analysis of TNF-alpha and proliferative cell nuclear antigen (PCNA) expression. RESULTS: Mean intimal thickness and volume (0.721+/-0.047 mm, 5.734+/-0.387 mm3 vs. 0.883+/-0.048 mm, 9.068+/-0.462 mm3) and intima/media volume ratio (0.70+/-0.05 vs 1.08+/-0.06) were significantly smaller in ETE (P<0.05). Western blotting showed a marked increase in TNF-alpha (203.15+/-5.29 vs. 494.49+/-6.11) and PCNA concentrations (152.66+/-7.37 vs. 175.53+/-4.36) in the ETS group. CONCLUSION: ETE anastomosis results showed significantly decreased inflammatory reaction and volume of intimal hyperplasia, and therefore seemed to be associated with better long-term graft patency.