Methylsulfonylmethane (MSM), which is one of the popular ingredients of so-called health foods in Japan, is expected to relieve inflammation in arthritis and allergies. However, there is no scientific evidence to confirm the efficacy and safety of MSM in detail. In this study, we examined the effects of MSM on cartilage formation in growing rats (G) and cartilage degradation in STR/Ort mice (A), an accepted human osteoarthritis (OA) model. For cartilage formation study, 6-week-old growing male Wister rats were assigned to four groups to receive a control or MSM-containing diet. To examine the efficacy of MSM on the cartilage of OA model mouse, 10-week-old male STR/OrtCrlj mice were assigned to three groups to receive a control or MSM-containing diet. The dosages used were amounts equal to the recommended supplements for humans [0.06 g/kg body weight (BW)/day: MSM1G and MSM1A], 10 fold higher (0.6 g/kg BW/day: MSM10G and MSM10A), and 100 fold higher (6 g/kg BW/day: MSM100G). Intake of MSM for 4 weeks did not affect cartilage formation in the knee joint in growing rats. Body, liver, and spleen weight in the MSM100G group were significantly lower than those in the control group. Intake of MSM for 13 weeks decreased degeneration of the cartilage at the joint surface in the knee joints in STR/Ort mice in a dose-dependent manner. These results suggest that appropriate intake of MSM is possibly effective in OA model mice; however, intake of large amounts of MSM induced atrophy of several organs.