AIDS,　caused　by　HIV-1,　is　one　of　the　most　dangerous　infectious　diseases　in　the　world.　Therefore,　it　is　necessary　to　develop　new　drugs　with　more　potent　bioactivities,　less　toxicity　and　higher　tolerability　for　controlling　the　viral　load,　particularly　by　using　the　raw　materials　that　are　widely　available.　Agaricus　blazei　Murill　(AbM),　known　in　China　as　jisongrong,　is　of　great　importance　as　a　food　source　and　as　a　health-promoting　supplement　for　immunomodulation.　The　polysaccharides　of　AbM　exhibit　various　biological　activities,　such　as　regulating　cellular　immunity　and　providing　anti-oxidative,　anti-infective,　and　anti-inflammatory　effects.　At　present,　to　our　knowledge,　no　report　has　explored　the　chemically　sulfated　and　anti-HIV-1　activity　of　AbM　polysaccharides.　Herein,　the　sulfated　AbM　polysaccharides　with　different　sulfur　contents　were　prepared　by　the　chlorosulfonic　acid-pyridine　method.　The　characteristics　of　sulfated　derivatives　were　established　by　the　determination　of　the　sulfur　content,　the　relative　molecular　weight,　and　the　Fourier-transform　infrared　spectroscopy.　The　anti-HIV　activities　of　the　sulfated　AbM　polysaccharides　were　evaluated　by　CCK-8　and　the　single-cycle　pseudovirus　infection　(TZM-bl)　assay.　The　sulfated　AbM　polysaccharides　had　strong　antiviral　properties,　and　the　half-maximal　inhibitory　concentrations　approached　that　of　the　positive　control,　azidothymidine.　Sulfated　modification　of　AbM　polysaccharides　can　increase　their　anti-HIV　pharmacological　activity,　which　makes　them　promising　alternative　candidates　as　bioactive　macromolecules　for　biomedical　applications　in　HIV/AIDS.