The study investigated the mechanism of sinomenine in mediating glycolysis inhibition to suppress inflammatory responses in rheumatoid arthritis rats through the adenosine monophosphate-activated protein kinase (AMPK)/silent information regulator 1 (SIRT1) signaling pathway. Rats were randomly divided into the control group , model group, sinomenine group , and sinomenine+AMPK inhibitor group.The degree of toe swelling was measured in each group, and the arthritis index was compared. The levels of inflammatory cytokines [interleukin-6 (IL-6), IL-1β and tumor necrosis factor-α (TNF-α)] in serum were detected by ELISA. Pathological changes in synovial tissue were examined using HE staining, while lactate content in synovial tissue was measured by spectrophotometry. Western blot was performed to detect the protein expression of AMPK, phosphorylated AMPK (p-AMPK), SIRT1, pyruvate kinase muscle isozyme M2 (PKM2), lactate dehydrogenase A (LDHA) and hypoxia-inducible factor 1α (HIF-1α) in synovial tissue. The results showed that compared with the control group, the model group exhibited significantly increased toe swelling, arthritis index scores, serum levels of TNF-α, IL-1β and IL-6, lactate content in synovial tissue, and protein expression of HIF-1α, PKM2, and LDHA in synovial tissue, while the p-AMPK/AMPK ratio and SIRT1 protein expression were significantly decreased (P<0.05). Compared with the model group, the sinomenine group showed significantly reduced toe swelling, arthritis index scores, serum levels of TNF-α, IL-1β and IL-6, lactate content in synovial tissue, and protein expression of HIF-1α, PKM2, and LDHA in synovial tissue, whereas the p-AMPK/AMPK ratio and SIRT1 protein expression were significantly increased (P<0.05). Compared with the sinomenine group, the sinomenine+AMPK inhibitor group demonstrated significantly elevated toe swelling, arthritis index scores, serum levels of TNF-α, IL-1β, and IL-6, lactate content in synovial tissue, and protein expression of HIF-1α, PKM2, and LDHA in synovial tissue, while the p-AMPK/AMPK ratio and SIRT1 protein expression were significantly decreased (P<0.05). These findings suggest that sinomenine can downregulate glycolytic activity, suppress inflammation, and alleviate symptoms in rheumatoid arthritis rats, potentially through activation of the AMPK/SIRT1 signaling pathway.