Abstract: OBJECTIVE To explore pathogenic distribution and expressions of transforming growth factor betal (TGF-β1)/signal transducer protein Smads (Smads) signaling pathways in elderly patients with chronic heart failure (CHF) and pulmonary infection. METHODS A total of 100 elderly patients with CHF and lung infection admitted to Tangshan Workers' Hospital between Jan and Jun 2021 were enrolled as the infection group, and another 100 elderly patients with CHF and without lung infection during the same period were enrolled as the control group. The clinical data of all patients were collected and pathogens were detected. The protein expression levels of TGF-β, Smad2 and Smad3, and serum levels of TGF-β1, interleukin-8 (IL-8) and tumor necrosis factor-α (TNF-α) between the two groups were compared. The correlation between the expression levels of TGF-β1/Smads signaling pathway-related proteins and cardiac function grading in New York Heart Association (NYHA) was analyzed by Spearman correlation analysis. RESULTS Total of 118 strains of pathogens in the infection group were isolated, including 69 strains (58.47%) of gram-negative bacteria, 40 strains (33.90%) of gram-positive bacteria and 9 strains (7.63%) of fungi. The protein expression levels of TGF-β1, Smad2 and Smad3, and serum levels of TGF-β1, TNF-α and IL-8 in the infection group were higher than those in the control group (P＜0.05). The expression levels of TGF-β1, Smad2 and Smad3 in the grade I-Ⅱ group were lower than those in the grade Ⅲ-Ⅳ group (P＜0.05). Correlation analysis showed that the expression levels of TGF-β1, Smad2 and Smad3 were positively correlated with NYHA grading (P＜0.05). CONCLUSION Gram-negative bacteria is the main pathogen in elderly patients with CHF and lung infection. TGF-β1/Smads signaling pathways may be over-activated, which may be related to impaired cardiac function.