Although CD163+ M2 macrophages were increased in the liver, and serum IL−6 levels were reduced in MSC−sEV treated animals, our data suggests that MSC−sEV treatment was efficacious in reducing liver fibrosis in a mouse model of NASH despite an increase in pro−fibrotic M2 macrophage polarization. Here, IL6 is linked to metabolic dysfunction-associated steatohepatitis.