Objective: To investigate the correlation between the liver kinaseB1/AMP-activated protein kinase pathway (LKB1/AMPK pathway) and atrial fibrillation (AF) in patients with mitral stenosis of rheumatic heart disease (RHD). Methods: A total of 40 patients with RHD who underwent valve replacement surgery were enrolled, including 20 with persistent AF and 20 with sinus rhythm (SR). Peripheral venous blood samples were taken before surgery and cardiac muscle tissue were taken from the right atrial appendages during surgery. ELISA was used to exam the level of hypersensitive C-reactive protein (hs-CRP) and thioredoxin (RTX) in peripheral venous blood. Real-time reverse transcription polymerase chain reaction (RT-PCR) was used to analyze the expressions of LKB1 and AMPK in the 40 patients. The correlation between AMPK, hs-CRP, RTX and LKB1 were analysed. Results: Compared with SR group, mRNA levels of LKB1 and AMPK were elevated in cardiac tissues from AF patients (P<0.05). The level of hs-CRP and RTX were also elevated in AF patients. Pearson correlation analysis showed that LKB1 was positively correlated with AMPK (r=0.373, P<0.05), and negatively correlation with hs- CRP, TRX (r=−0.546, −0.417, all P<0.05). Conclusion: LKB1/MAPK pathway may play an important role in the initiation and progression of AF through inflammation and oxidative stress.