The spread of Porcine contagious pleuropneumonia (PCP), a severe disease that occurs in pigs caused by Actinobacillus pleuropneumoniae (APP), remains a threat to the porcine farms and has been known to cause severe economic losses. Serum amyloid A (SAA) is an acute-phase protein rapidly expressed in response to infection and inflammation in vertebrates. This study aimed to investigate the function of SAA3 in bacterial infections. Here, APP was used to infect porcine alveolar macrophages (3D4/21), pigs, and mice. The results showed that the expression level of SAA3 was significantly up-regulated in APP-infected 3D4/21 cells, as well as pigs and mice infected with APP. In SAA3-overexpressing (SAA3-OE) cells, the expression of IL-1β, IL-6, and TNF-α were also up-regulated, while silencing of SAA3 reversed these effects. Furthermore, the levels of APP were substantially up-regulated in the culture supernatant of SAA3-OE cells, with significant down-regulation in siRNA-SAA3 cells culture supernatants. Also, SAA3-OE enhanced the adhesion and invasion of APP-infected target cells. These findings suggest that porcine SAA3 up-regulated cytokine expression, with increased SAA3 expression exacerbating inflammation. Notably, SAA3 promoted the growth of APP during the logarithmic growth phase. This created favorable conditions for APP growth and promoted its proliferation, adhesion, and invasion. These findings provide insights into the role of porcine SAA3 in the course of bacterial infection.