Interleukin (IL)-1β serves an important role in the promotion of the growth of osteoarthritis (OA) lesions. Paeoniflorin (PF) has been identified to exert anti‑inflammatory and anti‑arthritic effects. However, it is uncertain whether PF may affect the expression levels of inflammatory mediators in OA chondrocytes. Therefore, the objective of the present study was to determine the effects of PF on the expression levels of inflammatory mediators in IL‑1β‑stimulated human OA chondrocytes. The results of the present study determined that PF inhibited the production of nitric oxide and prostaglandin E2 induced by IL‑1β, and the expression of inducible nitric oxide synthase and cyclooxygenase‑2 in chondrocytes. Additionally, PF significantly inhibited the IL‑1β‑stimulated production of metalloproteinase‑3 (MMP‑3) and MMP‑13 in chondrocytes. PF inhibited the expression of nuclear factor‑κB (NF‑κB), p65 and NF‑κB inhibitor α degradation was induced by IL‑1β in chondrocytes. The results of the present study suggest that PF may inhibit IL‑1β‑induced expression of inflammatory mediators in human OA chondrocytes by suppressing the activation of the NF‑κB signaling pathway. Therefore, PF may be a potential agent in the future treatment of OA.