OK-432, a Streptococcus-derived anticancer immunotherapeutic agent, has been applied in clinic for manyyears and achieved great progress in various cancers. In the present study, we investigated its anticancer effecton bladder cancer through tumor associated macrophages (TAMs). MTS assay validated OK-432 could inhibitproliferation in both T24 and EJ bladder cell lines. OK-432 also induced apoptosis of bladder cancer cells in vitro.Consequently, we demonstrated that OK-432 could suppress the bladder cancer cells migration and invasion byaltering the EMT-related factors. Furthermore, using SD rat model, we revealed that OK-432 inhibited tumorgrowth, suppressed PCNA expression and inhibited metastasis in vivo. Taken together, these findings stronglysuggest that OK-432 inhibits cell proliferation and metastasis through inducing macrophages to secret cytokinesin bladder cancer.