This cross-sectional study aimed to investigate whether the infrapatellar fat pad (IPFP) mediates the relationship between environmental exposures and clinical symptoms in patients with knee osteoarthritis (KOA). A total of 108 participants with KOA were included in this study, and environmental exposure data, including temperature, wind speed, and relative humidity, were obtained from local meteorological records. IPFP characteristics were quantitatively assessed using 3.0T magnetic resonance imaging (MRI), including morphometric and signal intensity (SI) parameters. Clinical symptoms were evaluated using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Principal component analysis (PCA) was used to reduce dimensionality of IPFP MRI features. Mediation analysis was performed to examine whether IPFP parameters mediated the effect of environmental exposures on WOMAC scores. PCA revealed that SI parameters accounted for 56.87 % of the total variance in IPFP features, while morphometric parameters explained 16.65 %. Correlation analysis showed that most SI parameters (e.g., mean SI, SD SI) were significantly associated with WOMAC scores (ranging from r = 0.20 to 0.49, p < 0.05), in contrast to morphometric measures. Environmental exposures, particularly lower temperatures, higher wind speed, and daily weather changes, were significantly correlated with increased SI. Mediation analysis demonstrated that IPFP MRI parameters, particularly SI parameters, significantly mediated the effects of environmental exposures on pain and total WOMAC scores. The IPFP, particularly its SI characteristics, mediates the relationship between environmental exposures and clinical symptoms in KOA.