Curcumin has been proved to have antioxidant and antiinflammatory actions. We investigated the prophylactic effect of curcumin against the development of non-alcoholic fatty liver (NAFLD) disease in high fat diet (HFD)-fed rats. The study included three groups of rats, group I were fed low-fat diet, group II were fed HFD and group III were fed HFD and curcumin at a dose of 4 g/kg diet for 12 weeks. Liver triglycerides (TG), plasma TG, plasma total cholesterol (TC), liver cell gene expression of inflammatory mediators (NF-kB subunit1, TNF-α and IL6) and liver histology were evaluated. The study revealed a significant increase in liver TG, plasma TG and TC as well as liver cell gene expression of inflammatory mediators in group II compared to group I. Moreover, Group II rats showed distorted hepatic architecture and fat accumulation in hepatocytes. While, in group III, Liver TG, plasma TG and TC and liver cell gene expression of the inflammatory mediators decreased significantly compared to group II and there was a decreased fat accumulation in the hepatocytes. We concluded that curcumin had a protective effect on the liver of HFD fed rats.