With the increasing prevalence of the obesity epidemic, non-alcoholic fatty liver disease 
(NAFLD) represent the most common liver disease worldwide and one of the important causes 
of hepatocellular carcinoma development. Also, it is strongly associated with type 2 diabetes 
mellitus. Metabolic inflammation has been suggested to play a central role in NAFLD 
progression. Monocytes represent a key player in meta-inflammation. Circulating monocytes, 
adipose tissue macrophages (ATM), and liver resident macrophages have roles in NAFLD 
development and progression. Adipose tissue macrophages accumulate as a result of adipose 
tissue hypoxia, they produce huge amount of cytokines inducing insulin resistance and excess 
fat accumulation in the liver. In this review, we highlight the burden of NAFLD, its association 
to metabolic parameters and obesity, with illustration of obesity induced inflammation and 
pathogenic pathways involved in insulin resistance development. We pointed to the plasticity 
of circulating monocytes, phenotypic and functional alteration of their subsets in NAFLD, and 
the therapeutic approaches targeting macrophages and their effects on improvement of insulin 
resistance and NAFLD progression.