: Apoptosis and caspase-3 play an important role in the pathogenesis of sepsis. In this study, the authors monitored myocardial apoptosis and investigated caspase-3 protein expression change in rats with sepsis. In addition, we investigated the protective effect of glutamine (Gln) on myocardial injury in septic rats. A rat model of sepsis was established by intraperitoneal injection of lipopolysaccharide (LPS). Rats were divided into control group, endotoxin (LPS) group and LPS + Gln group, which were further divided into 4 subset groups (0, 6, 12 and 24 hour subgroups; n = 6). The rate of myocardial apoptosis, caspase-3 mRNA expression and caspase-3 protein expression were examined. Data were analyzed using the F-test or linear correlation test. The results revealed that the rate of myocardial apoptosis in the LPS group was significantly higher than that in the control group (P < 0.05). Compared with the control group, LPS group has an upregulated caspase-3 mRNA expression level. However, the caspase-3 protein was low expressed (P < 0.05). The LPS + Gln group has significant lower myocardial apoptosis rate compared with the LPS group (P < 0.05). In addition, caspase-3 mRNA expression levels and caspase-3 protein expression levels were lower in the LPS + Gln group (P < 0.05). We found that Gln reduces the extent of myocardial apoptotic cell death by decreasing the gene and protein expression of caspase-3. Therefore, Gln may be used to prevent the onset of sepsis at an early stage.