Heparin has been widely used as an anticoagulant for more than 80 years. However, there is now considerable evidence that heparin also possesses anti-inflammatory activity, both experimentally and clinically. Importantly in many instances, the anti-inflammatory actions of heparin are independent of anticoagulant activity raising the possibility of developing novel drugs based on heparin that retain the anti-inflammatory activity. Heparin exhibits anti-inflammatory activities via a variety of mechanisms including neutralization of cationic mediators, inhibition of adhesion molecules, and the inhibition of heparanase, all involved in leukocyte recruitment into tissues. It is anticipated that furthering our understanding of the anti-inflammatory actions of heparin will lead to the development of novel anti-inflammatory drugs for a variety of clinical indications. 1. Introduction Heparin has been used for over eighty years as an anticoagulant. Despite its widespread use, the exact mechanism for the anticoagulant activity of heparin was not elucidated until the 1960s and the specific polysaccharide sequence within the heparin molecule required for this interaction was not defined until nearly twenty years later [1]. The inherent nature of heparin being a polydisperse heterogeneous molecule continues to make this a complex material to work with. In addition to the well described anticoagulant effect of heparin, a range of polysaccharides, some derived from heparin, and some from related structures, have been found to interact with a wide variety of biological pathways and systems, raising the possibility that such drugs may have wider therapeutic uses than inhibiting coagulation. These other activities of heparin and related drugs are less well understood than anticoagulant activity, but such drugs are now under investigation for a wide range of clinical indications, particularly for the treatment of inflammatory diseases. Heparin is a polysaccharide, and heparin has several unusual characteristics. Firstly, it is polydisperse in nature; that is, it does not possess a defined single structure in the manner of a simple low-molecular-weight drug such as aspirin. Rather, heparin contains a range of saccharide chains of variable lengths and structural diversity and will typically have an average molecular weight of 14 to 18？kDa, but can contain polysaccharides from 10 to over 100 monosaccharide units [1]. The second feature is that heparin is a highly sulphated molecule, and due to this property has a very high negative charge which allows it to bind to a very
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