In the present study, the influence of autophagy on apoptosis of macrophage induced by Salmonella typhimurium was investigated. Murine macrophage-like cell line J774A.1 was cultivated with RPMI 1640 containing autophagy inducer rapamycin (RAPA) or not overnight, the standard Salmonella typhimurium virulent strain SR-11 was used as the test bacterium. First, the influence of RAPA on bacteria growth and J774A.1 cells survival were detected, then the incubation of J774A.1 and SR-11 were dynamically tracked 24 h. Cell ultrastructure, the formation of autophagic vesicles, Beclin-1 and Bcl-2 expression, cell survival rate, the number of intracellular viable bacteria and cell apoptosis were detected at different time. The results showed that RAPA didn’t affect bacteria growth and the survival of J774A.1 cells. However, in cellular infectious model, RAPA could significantly reduce the number of intracellular viable bacteria and the rate of macrophage apoptosis, thereby increasing cell survival (P < 0.05). Some bacteria was wrapped in the autophagic vacuoles of J774A.1 cells during inchoate infectious stage, and cellular ultrastructure was normal after RAPA treatment. Moreover, the expression of Beclin-1 was increased while the expression of Bcl-2 was declined, and cells damage were significantly lighter in the late stage. All these results suggested that the regulation of cellular autophagy to lower the level of host cells apoptosis may be used as new ways of the prevention and control for some infectious diseases.