Aim To explore the effects of yam polysaccharide (RDPS-Ⅰ) on myocardial injury and tyrosine protein kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway in septic rats. Methods Ninety rats were randomly divided into:RDPS-Ⅰ low (1.0 g/kg), medium (2.0 g/kg), and high (3.0 g/kg) dose groups, model group, positive control group and sham operation group. The cecal ligation and perforation method was used to establish a sepsis rat model, after the model was completed, RDPS-Ⅰ low, medium and high dose groups were given corresponding dose yam polysaccharide by gavage respectively; The positive control group was given 200 mg/kg subcutaneous injection of 4 mL/kg ampicillin solution; The other two groups were given normal saline, and intervened once every 12 hours, for 6 consecutive days. After the intervention, the hemodynamic indicators of the rats were measured, including mean arterial pressure (MAP), left ventricular systolic pressure (LVSP), and heart rate (HR); Hematoxylin-Eosin (HE) staining was used to observe the pathological changes of septic rat myocardium; TUNEL staining was used to detect cardiomyocyte apoptosis of septic rat; enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of inflammatory cytokines in septic rat serum; Western blot was used to test the expression level of JAK2/STAT3 signaling pathway proteins in rat myocardial tissue. Results Compared with the sham operation group, the myocardial tissue was disordered and occurred with severe inflammatory cell infiltration in the model group; LVSP, HR, MAP decreased by 56%, 54%, 55% (P＜0.05). The levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), and nuclear factor-κB (NF-κB) in serum and p-JAK2/JAK2, p-STAT3/STAT3 and apoptosis rates in myocardial tissue were increased by 2.5,1.4,1.9,1.9,2.6,2.26 and 3.67 times (P＜0.05), respectively. Compared with model group, the degree of myocardial tissue disorder and inflammatory cell infiltration were gradually relieved after RDPS-Ⅰ intervention; LVSP, HR and MAP increased by 0.4,0.35 and 0.34 times in low dose RDPS-Ⅰ group, respectively; TNF-α, IL-6, IL-1β, NF-κB, p-JAK2/JAK2, p-STAT3/STAT3 and apoptosis rate decreased by 28%, 19%, 18%, 26%, 27%, 29%, 25%, respectively. LVSP, HR and MAP increased by 0.2,0.67 and 0.83 times in medium dose RDPS-Ⅰ group, respectively. TNF-α, IL-6, IL-1β, NF-κB, p-JAK2/JAK2, p-STAT3/STAT3 and apoptosis rate decreased by 45%, 41%, 40%, 50%, 49%, 50%, 50%, respectively. LVSP, HR and MAP increased by 1.1,1.10 and 1.15 times in high dose RDPS-Ⅰ group (P＜0.05), respectively. TNF-α, IL-6, IL-1β, NF-κB, p-JAK2/JAK2, p-STAT3/STAT3 and apoptosis rate decreased by 64%, 63%, 63%, 66%, 70%, 66%, 70% (P＜0.05), respectively. Conclusion Yam polysaccharide can reduce inflammation, and improve myocardial injury and dysfunction in septic rats, which may be related to the inhibition of JAK2/STAT3 signaling pathway.