Background Previous studies about post-stroke peripheral structural remodeling have been focused on muscle fiber alterations, while extracellular matrix (ECM) remodeling in musculoskeletal tissues remains unclear. This study examines changes in extracellular matrix (ECM), specifically hyaluronan (HA) and collagen, in forelimb muscles following distal middle cerebral artery occlusion (dMCAO) in mice. Methods Twenty-two 8-week-old C57BL/6 mice (10 male, 12 female) were randomly assigned to the control group ( n = 10; 4 male, 6 female) or the experimental group ( n = 12; 6 male, 6 female). 4 weeks post-stroke, forelimb muscle samples were collected and analyzed for HA and collagen distribution and concentrations. Results HA concentrations were significantly elevated in both the left (stroke affected) forelimb muscles (63.74 ± 11.80 μg/g), and right (unaffected) forelimb muscles (64.16 ± 13.52 μg/g) of stroke mice compared to the controls (left: 50.07 ± 8.84 μg/g, p = 0.022; and right: 49.36 ± 12.22 μg/g, p = 0.015). No significant difference in HA levels was observed between the affected and unaffected sides of stroke mice ( p = 0.905). Collagen concentrations did not differ significantly among groups (control left: 8.62 ± 2.91 μg/g; control right: 8.77 ± 1.35 μg/g; stroke-affected: 8.24 ± 2.11 μg/g; stroke-unaffected: 8.28 ± 2.45 μg/g). Conclusion The results revealed a systemic increase in HA concentration in the stroke group, while collagen levels remained unchanged. These findings provide biochemical evidence of early alterations in extracellular matrix composition after stroke.