Background: The prevalence of obesity is increasing worldwide and recurrent attempts for losing weight are very common. Diet cycling predisposes to health hazards including non-alcoholic fatty liver disease (NAFLD). Aim: to evaluate the effect of diet cycling on the course of NAFLD. Materials and methods: Seventy-two male albino Sprague-Dawly rats were used in the study. Rats were equally divided into three groups: Normal rat chow diet (NCD) control group, high fat diet (HFD) group, and diet cycling group. NCD and HFD groups were kept on NCD and HFD respectively for the overall experimental period. Diet cycling group was fed with HFD for eight weeks to induce NAFLD, and then shifted to NCD for four weeks, followed by HFD for four weeks to allow rebound weight gain. By the end of eight, twelve and sixteen weeks, eight rats from each group were randomly selected and evaluated for body mass index (BMI), liver index, lipid profile, free fatty acids, liver enzymes, homeostasis model assessment index for insulin resistance (HOMA-IR) index, tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and transforming growth factor-β1 (TGFβ1).+ Hepatic oxidative stress enzymes were also measured. Liver histopathology and alphasmooth-muscle actin (α-SMA) immunoreactivity were evaluated. Results: Diet cycling group showed significant increase in BMI, Liver index, serum inflammatory markers, and concomitant significant decrease in hepatic glutathione peroxidase levels. In addition, marked fatty and inflammatory infiltrations were observed in diet cycling group. Conclusion: Diet cycling had a negative influence on NAFLD and interfered with normal liver function. These results suggest that rebound weight gain negatively affect the course of NAFLD.