Diabetic nephropathy (DN) is a common complication of diabetes mellitus which can result in renal failure and severely affect public health. Several studies have revealed the important role of podocyte injury in DN progression. Although, the involvement of exosomes derived from M2 macrophages has been reported in podocyte injury, the underlying molecular mechanism of M2 macrophage-secreted exosomes has not been fully elucidated. Our study suggests that M2 macrophages mitigate lipopolysaccharide (LPS)-induced injury of podocytes via exosomes. Moreover, we observed that miR-93-5p expression was markedly upregulated in exosomes from M2 macrophages. Inhibition of miR-93-5p derived from M2 macrophage exosomes resulted in apoptosis of LPS-treated podocytes. Additionally, TLR4 showed the potential to bind to miR-93-5p. Subsequently, we validated that TLR4 is a downstream target of miR-93-5p. Further findings indicated that silencing of TLR4 reversed the renoprotective effects of miR-93-5p-containing M2 macrophage exosomes on LPS-induced podocyte injury. In summary, our study demonstrated that M2 macrophage-secreted exosomes attenuated LPS-induced podocyte apoptosis by regulating the miR-93-5p/TLR4 axis, which provides a new perspective for the treatment of patients with DN.