Limb-girdle muscular dystrophy 2B (LGMD2B) stems from heterogenous mutations in dysf. Dysferlin is a critical muscle membrane protein and is associated with sarcolemma repair. Reduced repair capacity of the sarcolemma can lead to chronic inflammation, fibrosis, and fatty infiltrate of the affected muscles. Galectin-1 is a galactoside-binding protein that has been shown to increase membrane repair in dysferlin-null myotubes and myofibers. We hypothesize that Galectin-1 can also reduce markers of chronic inflammation in the NF-κB pathway. To do this, we employ immunoblotting, immunofluorescence, and flow cytometry to measure various markers of inflammation. Our results show that inflammation modulation is dependent on the oxidation and multimeric state of Galectin-1. In dysferlin-null cells, treatment with Galectin-1 decreases levels of inflammatory markers p65, p50, and TAK1 in the NF-κB pathway. The inflammatory inhibitor IKBα is increased after treatment with Galectin-1. We also show that the non-canonical pathway, NIK, is not impacted by Galectin-1 treatment. A one-week treatment with Galectin-1 in dysferlin-null mice resulted in a decrease in inflammatory macrophages (M1) and an increase in anti-inflammatory macrophages (M2). After a one-month treatment with Galectin-1, M1 macrophages remained reduced, although the M2 population also returned to saline-treated levels. The levels of p50 and p65 in muscles were also reduced during the one- month treatment. These results indicate that Galectin-1 treatment can attenuate some of the inflammatory response associated with LGMD2B, although the long-term response and mechanism of macrophage polarization remains to be tested. This strengthens the evidence that Galectin-1 may be useful in the treatment of LGMD2B.