Fructose-enriched diet (FED) is increasing worldwide. The study aims to investigate oxidative, histopathological, and immunohistochemical effects of fructose-enriched diet and swimming exercise on liver tissue in rats. Wistar rats were divided into 4 groups: Group I (Control), Group II (FED), Group III (FED+Exercise), and Group IV (Control+Exercise). MDA levels and enzyme activities of SOD and CAT were measured in liver tissue. Also, histopathological and immunohistochemical examinations (caspase-3, RANKL, TNF-α, and HSP-70) were performed on the liver tissue. MDA levels and SOD activities were found to be significantly higher in Group III compared to the other groups (p < 0.05). SOD activity was found to be lower in Group II compared to Group I (p = 0.035). CAT activities did not differ significantly between groups. While degeneration was noticed in Group II, normal tissue architecture was observed in other groups. Caspase-3, RANKL, and TNF-α expressions were higher in Group II than in the other groups, while HSP-70 expression was lower (p < 0.05). Fructose-enriched diet increases oxidative damage, degeneration, inflammation, and necrosis in the liver. In addition, a fructose-enriched diet is damaging to the liver by increasing the expressions of caspase 3, TNF-α, and RANKL and decreasing the expression of HSP-70. Swimming exercise largely restores these effects.