Background: Rhus toxicodendron (Rhus tox) is a homeopathic remedy with anti-inflammatory activities used for arthritis pain.Methods: We studied the effects of 4×, 30×, 30c and 200c homeopathic dilutions of Rhus tox in primary cultured mouse chondrocytes. We examined the expression of collagen type II, a marker protein of chondrocytes, and cyclooxygenase-2 (COX-2), which is responsible for the biosynthesis of prostaglandin E2 (PGE2) and the regulation of the inflammatory response. We assessed the expression of collagen type II and COX-2 using biochemical and immunological methods, such as reverse transcription polymerase chain reaction (RT-PCR), quantitative (or real-time) RT-PCR (qRT-PCR) and immunoblot assays.Results: Stimulation with different concentrations of Rhus tox increased the mRNA expression of COX-2, and stimulation with 30× Rhus tox showed the most prominent mRNA expression in both RT-PCR and qRT-PCR analyses. We also observed that homeopathic dilutions of 4×, 30× and 30c Rhus tox inhibited collagen type II expression, suggesting that Rhus tox induced the dedifferentiation of chondrocytes. In addition, treatment with 30× Rhus tox significantly increased PGE2 release compared with other homeopathic dilutions of Rhus tox.Conclusions: Taken together, these results suggest that homeopathic treatment with Rhus tox induced chondrocyte dedifferentiation and inflammatory responses, such as COX-2 expression and PGE2 production, in primary cultured chondrocytes.