More studies have indicated that polysaccharide sulfate has anti-coagulant activity. Now, heparin is the most popular anticoagulant used in clinic, however, its side effects have also caused highly concern. It is still under intensive investigations to synthesize effective safe polysaccharide sulfate as heparin substitute. We extracted water-soluble polysaccharide from fermented mycelium of edible polyporus albicans(Imaz.) teng, and got the water-soluble polyporus albicans teng sulfate(PATS) by modifying the water-solubility polyose with the method of chlorosulfonic acid-pyridine. The anti-coagulant assay of PATS in vitro towards normal human plasma indicates its remarkable anticoagulant activity, while the dose could be as low as 5 mg/L for anticoagulation. The anti-coagulant effect was equivalent to that of heparin about 150 U when the concentration of PATS was 10 mg/L. The study on anti- coagulation mechanism suggests that PATS got involved in the intrinsic pathway. The anti-coagulation activity of PATS was due to the inhibition of the coagulation factors IIa and Xa activities mediated by antithrombin III(ATIII). The anti-coagulation mechanism of PATS is absolutely identical to that of heparin. In conclusion, we suggest that PATS has the similar anti-coagulation characteristic to heparin, but with a better anti-coagulation effect. Meanwhile, derived from edible fungus-polysaccharide, PATS has more bio-safety advantage. Therefore, PATS has promising future to be developed and used as an ideal substitute for heparin in clinic.