BACKGROUND: The traditional Chinese recipe "Erjing Formula", composed of HuangJing and GouQi, is recognized for its tonifying and revitalizing properties, but the active components responsible for these effects are poorly explored. This study investigated the antifatigue effects of Erjing Formula polysaccharides (EJFP). METHODS: Mice were treated with EJFP and subjected to weight-loaded swimming tests. Biochemicals were measured, while muscle changes were analyzed by H&E staining and protein expression by Western blotting. OBJECTIVE: The present study aimed to investigate the anti-fatigue effects of EJFP through weight-loaded swimming tests in mice. METHODS: SPF-grade healthy male rat species KM mice were gavaged with EJFP and then subjected to a weight-loaded swimming test. Later, the levels of various biochemical indicators, including blood lactate (BLA), blood urea nitrogen (BUN), superoxide dismutase (SOD), malondialdehyde (MDA), muscle glycogen (MG), and hepatic glycogen (HG), were measured. The muscle tissue slices were analyzed using hematoxylin and eosin H&E) staining. Additionally, the expression levels of Kelch-like ECH-associated Protein 1 (Keap-1) and nuclear factor erythroid 2-related factor 2 (Nrf2) in the muscle tissue of each group were detected using Western Blotting. RESULTS: EJFP (Erjing Formula Polysaccharides) significantly increased swimming time (p ≤ 0.01), reduced oxidative stress markers and detrimental metabolites (BLA, BUN, and MDA), and elevated SOD, MG, and HG levels. Histologically, it improved muscle integrity. Nrf2 expression increased, indicating a relationship between antioxidant effects and antifatigue activity. CONCLUSION: EJFP demonstrated anti-fatigue effects, mainly at moderate doses, by modulating the Nrf2/Keap1 pathway and improving glycogen and antioxidant levels. This is the first study to document the anti-fatigue effects of Erjing Formula polysaccharides, establishing a theoretical basis for practical applications in the development of anti-fatigue products.