The ultimate goal of this study is to investigate the bimolecular changes in a rat model of high fat diet induced Nonalcoholic fatty liver disease (NAFLD). Also, the lipotropic, antioxidant and anti-inflammatory effects of spirulina platensis treatment were clarify through evaluation of certain biochemical and molecular parameters in the blood and liver tissue of rats. Twenty one adult white albino rats were separated into three groups. Group I (Normal control): received no drugs and balanced diet, Group II (NAFLD- induced group): rats fed high fat diet for 8 weeks followed by normal basal ration feeding for another 8 weeks. Group III (NAFLD + spirulina): rats treated with spirulina orally at a dose of (150 mg/kg b.wt/day) for 8 weeks after induction of NAFLD. The obtained results showed a significant increase in serum total cholesterol (TC) and triacylglycerols (TAG) concentrations with significant up-regulation of liver gene expression TNF-α, IL-1β, NF-kβ, PPAR-α, ACC, FAS and SREBT-1in NAFLD- induced rats. Also, various histopathological alterations were detected in liver tissue of induced NAFLD rats. Treatment with spirulina in NAFLD-induced rats parameters measured near the normal level of rats group (G1). Also, spirulina potentially improved molecular hepatic function alterations related to NAFLD. Interestingly, histopathological findings supported that spirulina markedly attenuates harmful effects of NAFLD and protects liver tissue. We conclude that, spirulina has a great role as antioxidant, anti-obesity and anti-inflammatory via inhibition of liver lipid metabolic disturbance, steatosis and oxidative stress singling.