Objective To investigate the effects of thermal stimulation on pain mediators and cartilage metabolism in patients with knee osteoarthritis. Methods A total of 80 patients with knee osteoarthritis admitted to the Department of Orthopedics, Fuzhou Traditional Chinese Medicine Hospital from February 2022 to February 2025 were selected as study subjects. The patients were randomly divided using a random number table into a control group （treated with etoricoxib tablets and sodium hyaluronate） and an observation group （additionally treated with an infrared therapy device）, with 40 patients in each group. The differences in bone metabolism and cartilage repair factors, and pain mediator levels between the two groups before and after treatment were compared. Results After treatment, compared with the control group, the observation group had higher levels of bone alkaline phosphatase （BALP）, bone glutamyl protein （BGP）, transforming growth factor-β （TGF-β）, and fibroblast growth factor-2 （FGF-2）, and lower levels of tartrate-resistant acid phosphatase-5b （TRACP-5b） （P<0.05）. After treatment, the levels of pain mediators in the observation group significantly decreased, including substance P （SP）, bradykinin （BK）, and prostaglandin E2 （PGE2） compared with the control group （P<0.05）. Conclusion Thermal stimulation can effectively improve bone metabolism and cartilage repair factor levels in patients with knee osteoarthritis, while significantly reducing pain mediator levels. This treatment plan has good analgesic and cartilage protective effects, and is worth promoting and applying in clinical practice.