The endoglycosidase heparanase1 (HPSE1)^1,2 is known to be involved in tumour cell migration.³ HPSE1 selectively cleaves heparan sulphate proteoglycans, which are ubiquitously expressed and form a major component of sub-endothelial matrix, as well as being strongly expressed on the surface of endothelial cells and circulating blood elements. The metastatic potential of tumour cells correlates with HPSE1 expression³ and inhibition of this enzyme has been demonstrated to reduce tumour cell adhesion, migration and colonisation.^3,4 Fewer studies have looked at the role of this enzyme in inflammation. However, leucocytes express heparanase, which is thought to facilitate their trafficking to sites of tissue inflammation and heparan sulphate influences the biological effects of an array of proteins, including chemokines and growth factors, involved in the inflammatory response.⁵ In the present study, we investigated the effects of recombinant HPSE1, pro-HPSE1 (inactive precursor) and enzymatically inactivated HPSE1, on inflammatory cell recruitment to the peritoneal cavity and leucocyte-endothelial interactions in the mesenteric microcirculation of the rat. Intraperitoneal injection of HPSE1 (500 µg) induced a significant inflammatory cell infiltrate, assessed 4 h later by peritoneal lavage immediately post mortem (1.05 ± 0.24 x 10⁶ vs 0.28 ± 0.04 x 10⁶ cells ml^-1 saline control; n=6 per group, P<0.05). This was similar in magnitude to the response to IL1β (20 ng; 1.12 ± 0.28 x 10⁶ cells ml^-1) but co-administration of HPSE1 and IL-β did not elicit a greater response than either stimulus alone. Intravital microscopy of the mesenteric microcirculation, under terminal anaesthesia, 4 h post-HPSE1 injection, showed an increase in rolling cell flux (35 ± 2.9 vs 15 ± 2.1 rolling cells min^-1 saline control; P<0.05) and adherent cells (30.3 ± 2.0 vs 3.5 ± 0.7 adherent cells per 100 µm saline control; P<0.05) in post-capillary venules (n=6 animals per group). Again, these responses were similar to those elicited by IL-1β (38 ± 1.8 rolling cells min^-1, 36.5 ± 2.9 adherent cells per 100 µm) and were sensitive to heparin, a non-selective inhibitor of HPSE1 activity. Pro-HPSE1 had similar effects to the active enzyme with respect to leucocyte accumulation in the peritoneal cavity, suggesting that the exogenously administered pro-enzyme is effectively processed to the active form in vivo. Finally, we further demonstrated a requirement for HPSE1 enzymatic activity in our model by assessing the effects of heat-inactivated enzyme in peritoneal lavage experiments, which had no effect on cell recruitment. Our data further indicate a role for heparanase in leucocyte recruitment, suggesting this enzyme to be a potential therapeutic target in inflammatory disease.