Persistent Chlamydia trachomatis infection is a risk factor for tubal infertility, and the pathology is largely due to the inflammatory response; however, the underlying molecular mechanism remains to be elucidated. MAP4K4, which has been implicated in inflammation, was upregulated in Chlamydia persistent infection in our previous study. Here, we employed both in vitro and in vivo models to evaluate the role of MAP4K4 in Chlamydia infection. We demonstrated that MAP4K4 promoted Chlamydia infectivity and increased survival in the genital tract of mice and had a palliative effect on acute inflammation. Additionally, it was beneficial to the development of chronic oviduct lesions. Mechanistically, MAP4K4 downregulated cytokine secretion, regulating the bactericidal effect of the inflammatory response. In addition, MAP4K4 negatively regulates T cell immunity by reducing the proportion of CD8+ T cells and the secretion of IFN-γ and TNF-α by T cells. Thus, these data suggest that MAP4K4 is essential in regulating the host immune response that controls Chlamydia replication, driving the inflammation that causes complications such as infertility. This work provides a novel target for adjuvant therapy of Chlamydia infection.