Wnt5a belongs to the large WNT family of cysteine-rich secreted glycoproteins, which is involved in multiple signaling pathways that regulate a variety of cellular processes, including cell motility, proliferation differentiation and so on during development. The regulation and signaling transduction of Wnt5a have been reported to closely relate to inflammatory response, which indicates that Wnt5a plays a critical role in the occurrence and development of inflammatory diseases. In this review, we summarized data on Wnt5a and its signaling pathway, as well as their involvement in inflammatory response. Further comprehensive understanding of the function and relationship between Wnt5a and inflammatory response would help us to develop novel diagnostic and therapeutic strategies for prevention and treatment of inflammatory diseases.