Nonalcoholic fatty liver disease (NAFLD) is a complex disease caused by a number of different pathogenic processes as a result of the systemic interaction between the liver and several other organs. Grape seeds proanthocyanidins extract (GSPE) potency in the liver is associated with improvement of the hepatic enzyme activities as their powerful antioxidant property results from its ability to directly scavenge free radicals and/or chelate metals. 32 male albino rats were assigned into 4 equal groups of 8 rats: 1. Normal control group (G1) of rats provided with standard normal diet for 12 weeks, 2. NAFL group (G2) of rats received high fat diet (HFD)-feeding for 6 weeks for induction of NAFL, followed by normal feeding for other 6 weeks, 3. GSPE treated group (G3) of the HFD-induced NAFL, followed by administration of GSPE for 6 weeks else, 4. GSPE and antiplatletes drug (Clopidogrel) co-treated group (G4), of the NAFL rats, followed by administration of GSPE and clopidogrel co-treatment for another 6 weeks. The results revealed that GSPE alone or with clopidogrel treatment significantly decreased serum AST, ALT and γGGT (G3, 4) that were significantly increased in HFD-NAFL rats (G2), and showed significant upregulation of IL1β, PPARα, TGFβ1 and TIMP1 in livers of NAFL rats (G2), that was significantly downregulated following administration of GSPE alone (G3), or with clopidogrel (G4). Subsequantly, treatment with GSPE alone or with antiplatelet drug can improve the metabolic disruptions associated with the induction of NAFL by improving the liver biomarkers and inflammatory mediator's expressions.