Abstract: Objective: To explore the antioxidant mechanism of Shanxi aged vinegar on rats induced by high fat diet based on PI3K/AKT1 pathway. Methods: Thirty SPF male Wistar rats were randomly divided into 5 groups: Normal group (C, conventional diet), high fat model group (M, high fat emulsion), low (LV), medium (MV) and high (HV) Shanxi aged vinegar intervention groups (1.35, 2.7, 5.4 g/(kg·bw)). Modeling (5 weeks) at the same time given Shanxi aged vinegar intervention, the aged vinegar intervention continued for 5 weeks. Serum lipid content, liver injury index and antioxidant enzyme activity were detected. The histopathological status of liver was observed by HE staining. The mRNA and protein levels of PIK3CA and AKT1 in rat liver were detected by qRT-PCR and Western blotting, and the localization was analyzed by immunohistochemistry. Results: Compared with group C, liver steatosis was severe in group M, serum lipid content and degree of liver injury were significantly increased (P<0.01), antioxidant enzyme activity was significantly decreased (P<0.01), mRNA and protein expressions of PIK3CA and AKT1 in liver tissue were significantly increased (P<0.01). The hyperlipidemia rats were successfully modeled and PI3K/AKT1 pathway was activated. The results of Serological showed that Shanxi aged vinegar could significantly down-regulate serum lipid content, improve liver injury, increase antioxidant enzyme activity (P<0.05), and reduce pathological injury of liver tissue, and the improvement effect of HV and MV groups was better than that of LV group. The results of qRT-PCR, Western blotting and immunohistochemical detection showed that PIK3CA and AKT1 were mainly located in the cytoplasm and nucleus of liver cells. Shanxi aged vinegar could significantly down-regulate the mRNA and protein expressions of PIK3CA and AKT1 in PI3K/AKT1 pathway (P<0.01), and the intervention effect of HV and MV groups was better than that of LV group. Conclusion: Different doses of Shanxi aged vinegar can improve lipid, antioxidant and liver function indexes of rats with high fat diet to different degrees, and the best dose may be between 2.7~5.4 g/(kg·bw). Shanxi aged vinegar may play a role in anti-oxidative stress injury by regulating PI3K/AKT1 pathway, so as to improve hyperlipidemia induced by high fat diet in rats.