Hyaluronan (HA) is one of polysaccharides in living body that is found widely in connective tissue of the mammals. It has no sulfate group but high molecular weight in comparison with other glycosaminoglycans (GAGs). We synthesized sulfated HA (S-HA) with various degrees of substitution (D.S.) in order to give HA new biological functions, since GAGs with sulfate groups interact with various biocomponents to express some specific biofunctions. Moreover in order to develop biomedical polymers, immunological response against artificial polymer matrices must be evaluated. So we measured histamine release from the mast cell and discussed the effect of S-HA on the immunological response. It was confirmed that they could be used as biomedical materials with immunological safety. And S-HA inhibited the histamine release that was induced by compound 48/80 from the mast cell. The inhibitory effect of S-HA was seemed to be due to such various factors as D.S., molecular weight, substitution site of the sulfate group and the structure of a polysaccharide chain.