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Abstract Background Telmisartan is a non-peptide angiotensin II receptor antagonist which acts by ACE/AngII/AT1 axis blockade (ARB). In the last years increasing evidence of its metabolic benefits pointed out this drug as the most promising ARB for nonalcoholic fatty liver disease (NAFLD) treatment. The aim of the present study was to investigate the Telmisartan effect on treating NAFLD in mice fed with a high-fat diet evaluating liver gene modulation. Twenty-four male mice were divided into four groups and fed for 60 days with a standard diet (ST), standard diet plus TEL (ST+TEL 5 mg/kg/day by gavage for 4 weeks), high-fat diet (HFD), or high-fat diet plus TEL (HFD+TEL 5 mg/kg/day by gavage for 4 weeks). Body weight, lipid profile, insulin, alanine transaminase, and aspartate aminotransferase were evaluated. Liver histology was analyzed. US imaging was performed to access liver dimension and echogenicity and also epididymal fat pad thickness. The expression of proinflammatory resistin/TRL4/MYD88 pathway was analyzed. Results The main findings showed that TEL reduced the resistin, TRL4, and Myd88 liver expression in the HFD + TEL group when compared to the obese control group (HFD). Decreased hepatic steatosis in the HFD + TEL group demonstrated by US measurements of the liver longitudinal axis and echogenicity were observed. In addition, TEL reduced epididymal adipose pad thickness, body weight, transaminases, and improved glucose tolerance test and HDL cholesterol. Conclusions We observed that Telmisartan treatment improved metabolism, decreasing NAFLD. Graphical Abstract Telmisartan improves metabolic and lipid profile and liver steatosis of obese mice