This research was conducted to investigate if there is a relation between insulin resistance incidence and inhibition of interferon gamma production or not. Firstly, insulin resistance was induced by high fat diet (HFD) intake for 6 weeks. Secondly, berberine was used as protective/curative compound for insulin resistance. Results revealed that feeding rats HFD for 6 weeks developed features of insulin resistance (IR) syndrome. These features presented in increased body weight, hyperglycemia, hyperinsulinemia, hypercholesterolemia (with increased LDL-cholesterol and decreased HDL-cholesterol), and hypertriglyceridemia. Level of antioxidant enzymes in HFD group was higher than in normal one. Also there was an increasing in level of proinflammatory cytokines as interleukin- (IL-) 6 and IL-12 in HFD group. Feeding rats HFD for 6 weeks also decreased level of interferon gamma (IFN-γ). The decreased level of IFN-γ has been shown to predict infection with infectious diseases especially viral infection. Treatment and protection with berberine 50 mg/kg/day for 2 weeks were found to be effective against the features of insulin resistance syndrome, improved levels of insulin resistance parameters, lipid profile, antioxidant enzymes, proinflammatory cytokines, and IFN-γ.