Objective: Previous studies have reported that Non-alcoholic fatty liver disease (NAFLD) is relevant to insulin resistance, and autonomic blockade improves insulin sensitivity. The current study aimed to evaluate the effect of propranolol as a beta-blocker on insulin resistance and biochemical parameters in the rat model of non-alcoholic fatty liver disease. Materials and Methods: Male Sprague-Dawley rats were divided into three groups (n= 8 in each group): normal control group (NC), high-fat diet group (HFD), and HFD and propranolol group (HFD+P). After six weeks, the rats were sacrificed and blood was collected for measurement of biochemical and ELISA analyses and also liver for hepatic biochemical indices. Liver tissue was collected for measurement of GLUT4 expression by immunoblot analysis. Results: After six weeks, the plasma level of triglyceride (TG), alanine aminotransferase (ALT), aspartate aminotransferase (AST), insulin resistance, TNF-α, hepatic content of malondialdehyde (MDA), and triglyceride (TG) increased in HFD group. Treatment by propranolol significantly attenuated these alterations. Conclusions: Administration of propranolol decreased insulin resistance, improved dyslipidemia, and increased expression of GLUT4 in the liver of rats.