Recent studies have suggested that puerarin may impede osteoclastogenesis and facilitate bone regeneration, in addition to attenuating tissue inflammation. The present study investigated the therapeutic effects of puerarin on inflammatory responses and monocyte recruitment in in vitro and in vivo osteoarthritis (OA) models. Puerarin treatment increased the proliferation of OA chondrocytes, as determined by Cell Counting Kit‑8 assay. In addition, the present results suggested that puerarin suppressed the interleukin‑1β‑induced production of inflammatory cytokines in OA chondrocytes and monocytes/macrophages, as assessed by ELISA. In a mouse model of mono‑iodoacetate‑induced OA, the present histological analyses suggested that administration with puerarin attenuated the inflammatory profile of OA joints and reduced cartilage destruction. Using flow cytometry, a decreased number of myeloid‑derived C‑C chemokine receptor 2+/lymphocyte Ag 6C+ monocytes was identified in the blood of OA mice treated with puerarin compared with control OA mice. Furthermore, quantitative real‑time polymerase chain reaction analysis suggested that puerarin treatment decreased C‑C chemokine ligand 2 expression in arthritic tissues. Collectively, the results suggested that puerarin treatment limited the recruitment of inflammatory monocytes. In summary, the present study provided pre‑clinical evidence that puerarin may serve as a potential target in the treatment of OA.