The development of chronic liver diseases is mediated by sustained hepatic inflammation. Our objective was to characterize the molecular mechanisms responsible for the hepatic inflammatory response to time limited TNF and IL-1 expression. C57Bl/6 mice were injected with 2x10⁷ plaque forming units intraperitoneally of an adenoviral vector containing TNF or IL-1 (AdTNF or AdIL-1). A nonreplicating adenoviral vector served as control. Four days later, under ketamine and xylazine anesthesia, the liver microvasculature was examined by intravital microscopy. In the post-sinusoidal venules, leukocyte rolling increased significantly in response to both AdTNF and AdIL-1, compared to controls. This response was significantly reduced following injection of an anti-₄-integrin monoclonal antibody (mAb). Post-sinusoidal rolling was further reduced to baseline following injection of an anti-P-selectin or anti-L-selectin mAb. Sinusoidal adhesion was greater in mice treated with AdIL-1 than AdTNF. Blocking ₄-integrin, P-selectin or L-selectin had no significant effect on sinusoidal or post-sinusoidal adhesion. In separate experiments, we administered AdTNF or AdIL-1 to mice deficient in ICAM-1. In ICAM-1-/- mice, post-sinusoidal leukocyte rolling significantly increased following IL-1b expression but not TNF. AdIL-1 but not AdTNF mediated sinusoidal adhesion was ICAM-1 dependant. AdTNF-induced sinusoidal adhesion was significantly reduced following 4 days of anti-MIP-2 mAb and anti-KC mAb. Prolonged expression of the cytokines TNF and IL-1 increases hepatic leukocyte-endothelial cell interactions. Interestingly, the mechanisms through which these cytokines bring about adhesion within the sinusoids differ; AdIL-1 sinusoidal adhesion uses an ICAM-1-dependent mechanism whereas AdTNF-mediated adhesion is ICAM-1 independent but CXC chemokine dependent.