Background: Complications of non-alcoholic fatty liver disease (NAFLD) include 67% of the criteria for metabolic syndrome. Acalypha indica L., (AI) which is one of a herbal plant had been known as anti-oxidant and anti-inflammatory effects. The effect of AI for therapy investigated by looking of the immune defense mechanisms. This researched was assessed by molecular docking approached on TLR9, NFκB, TNFα expression and liver morphological changes. Methods: Animal models of steatohepatitis were collected from high-fructose and cholesterol diet (HFCD) of Sprague-Dawley rats for 12 weeks and followed by therapy for 8 weeks. There were 5 groups from twenty five researched rats, include normal group (K1), HFCD group (K2), HFCD group supplemented with 400 mg Acalypha indica L. (K3), combination between 400 mg AI+Gemfibrozil (Gem) 31 mg (K4) and Gem 31 mg/kg (K5) in kgBW, respectively. Results: The results of molecular docking were carried out by assessing the interaction between hydrogen molecules of AI compounds and amino acid residues in TLR9, NFκB, TNFα. Morphological changes were assessed by scoring system. Statistical analyzed used Kruskall Wallis with post hoc Mann Whitney test continued by Spearman correlation test. Conclusion: The molecular docking analysis showed that, an alkaloid compounds were found besides the flavonoid compounds that can bind to the binding pocket of inflammatory markers with the best binding energies. Other compounds, there are dasycarpidan-1- methanol, acetate (ester), fenofibrate and quinine. Supplementation of AI would reduced hypertrophy (p=0.031), macrovesicular steatosis (p=0.018), inflammation foci (p=0.005) and also decreased of TLR9 (p=0.009), NFκB (p=0.009), TNFα (p=0.009) expression, but not as good as the combination of AI+Gem. © 2022 Phcogj.Com.