The effects of Ganoderma lucidum spore oil (GSO) on liver fibrosis in rats induced by carbon tetrachloride (CCl₄) combined with high-fat diet was investigated, and its potential mechanism was explored. Male SPF SD rats were divided into blank control group, model control group, positive drug group, and GSO low, medium and high dose groups. The liver fibrosis model was induced by CCl₄ combined with high-fat diet for 6 weeks, and GSO was administered for 8 weeks at the same time. The protective effect of GSO on liver fibrosis was evaluated by detecting the serum physiological and biochemical indexes, morphology of rat liver slices , oxidative stress, and fibrosis related proteins of rat liver tissue. The results showed that GSO could significantly improve the survival rate of rats with liver fibrosis, making the survival rate recover to the level of the blank control group. The results of pathological staining showed that the liver tissue structure was improved in different degrees in each group, and the proportion of collagen area and areal density in the GSO middle and high dose groups was significantly decreased. The high dose group could significantly reduce the levels of plasma liver function-related indexes, the contents of liver fibrosis indexes. Meconwhile, GSO high dose group significantly decreased the content of MDA, increase the content of GSH, the activity of SOD survival status, liver fibrosis, and the expression of MMP-9. The results showed that middle and high dose of GSO (15 and 30 fold recommended dosage of human body) could improve the survival rate and antioxidant capacity of liver fibrosis model rats and had the protective effect on rat survival rate and liver fibrosis.