Proteoglycans (PGs) are abundant components of the extracellular matrices (ECM) of skeletal muscle. We have previously found that the synthesis of skeletal muscle PGs present at the ECM increase after denervation. The experiments reported here were undertaken to identify which PG(s) increase after denervation of rat leg muscles. Incorporation of radioactive sulfate demonstrated the presence of a chondroitin/dermatan sulfate PG of 70-90 kDa in the skeletal muscle ECM, which increased after denervation. The PG has a core protein of 39-45 kDa after treatment with chondroitinase ABC. Antibodies against rat decorin, a chondroitin/dermatan sulfate PG synthesized by various cell types, specifically immunoprecipitated this PG from a mixture of PGs. Immunocytolocalization of this PG indicated that the chondroitin/dermatan sulfate PG accumulates at the perimysium of skeletal muscle after denervation. Finally, Northern blot analysis indicated an increase of muscle transcripts for decorin after denervation. The data reported here suggest that a chondroitin/dermatan sulfate PG present at the skeletal muscle ECM, very similar if not identical to decorin, increases after denervation.