B cells are crucial mediators of immune homeostasis. Their interaction with and functional relevance for angiogenesis in muscle ischemia, however, have remained unclear and are the focus of the present study. We investigated their role by inducing muscle ischemia in B cell-deficient J_HT and wildtype control mice via femoral artery ligation (FAL). Ischemic gastrocnemius muscles were harvested 7 days after FAL and analyzed by (immuno-)histology. B cell-deficient mice displayed aggravated ischemic tissue damage, as evidenced by H&E staining. In addition, angiogenesis was impaired in B cell-deficient mice, as demonstrated by a reduced capillary-to-muscle fiber ratio, and decreased endothelial cell proliferation (CD31⁺/BrdU⁺). Moreover, B cell-deficient mice showed increased macrophage (CD68⁺) infiltration with a predominance of pro-inflammatory M1-like polarized macrophages (CD68⁺MRC1⁻) and a corresponding reduction in regenerative anti-inflammatory M2-like polarized macrophages (CD68⁺MRC1⁺). In summary, our data on B cell deficiency identifies B cells as potential regulators of ischemia-induced angiogenesis, most likely by influencing macrophage infiltration and polarization toward a regenerative M2-like polarized phenotype in muscle tissue ischemia.