Nonalcoholic fatty liver disease (NAFLD) has become a major health problem in developed countries. It has affected more than 30% of the general population and is commonly associated with insulin resistance, which is a major risk factor for the development of type 2 diabetes and a central feature of the metabolic syndrome. Furthermore, accumulating evidences reveal that NAFLD as well as insulin resistance is strongly related to inflammation. Cytokines and adipokines play a pivotal role in inflammatory processes. In addition, these inflammatory mediators regulate various functions including metabolic energy balance, inflammation, and immune response. However, their role in modulating ectopic lipids involved in the development of insulin resistance, such as diacylglycerols and ceramides, remains unknown. The aim of this review is first to describe the pathophysiology of insulin resistance in NAFLD. In particular, we discuss the role of ectopic lipid accumulation in the liver. Secondly, we also summarize recent findings emphasizing the role of main inflammatory markers in both NAFLD and insulin resistance and their potential role in modulating hepatic fat content in NAFLD and associated hepatic insulin resistance.