Inflammatory responses involve the action of inflammatory mediators that are necessary for the clearance of invading bacterial pathogens. However, excessive production of inflammatory mediators can damage tissues, thereby impairing bacterial clearance. Here, we examined the effects of Weigela florida on the expression of inflammatory cytokines induced by Pseudomonas aeruginosa or Staphylococcus aureus infection in macrophages. The results showed that pre-treatment with W. florida markedly downregulated the bacterial infection-mediated expression of cytokines. Additionally, post-treatment also triggered anti-inflammatory effects in cells infected with S. aureus to a greater extent than in those infected with P. aeruginosa. Bacterial infection activated inflammation-associated AKT (Thr308 and Ser473)/NF-κB and MAPK (p38, JNK, and ERK) signaling pathways, whereas W. florida treatment typically inhibited the phosphorylation of AKT/NF-κB and p38/JNK, supporting the anti-inflammatory effects of W. florida. The present results suggest that W. florida decreases the infection-mediated expression of inflammatory mediators by inhibiting the AKT/NF-κB and MAPK signaling pathways, implying that it may have potential use as an inhibitory agent of excessive inflammatory responses.