Osteoarthritis (OA) is a multifactorial disease associated with pathological changes in a wide variety of musculoskeletal tissues, including articular cartilage degeneration, synovitis, ligament tears as well as muscle wasting. Cartilage is known as a predominant pathology, however the association between the pathogenesis of OA around the knee joint tissues and pain is limited. Infrapatellar fat pad (IFP) fibrosis and muscle atrophy are the main features of chronic OA phenomenon that cause joint pain, stiffness and impairment of skeletal muscle, which contributing to locomotor restriction in OA patients. Despite a high prevalence of knee OA, there is still a lack of comprehensive information explaining the interplaying mechanisms among these OA features. Although various animal models of OA have been characterized, none of them can truly represent all aspects of the OA features. Monoiodoacetate (MIA)‐induced OA is one of the most common animal model used in the OA research, in which intra‐articular injection of MIA can lead to articular cartilage destruction and development of pain‐like behaviour. This study aimed to characterize and determine the suitable time point, at which MIA could significantly induce the development of IFP fibrosis and hind limb muscle atrophy in this OA rat model. IFP and soleus muscle were collected for histological analysis at 4 and 8 weeks post‐OA induction. In addition, pain‐related behavior was also evaluated using hind limb weight distribution test. Semi‐quantitative analysis of Masson’s trichrome staining revealed that the percentage of IFP fibrosis area was not significantly different at 4 weeks compared to 8 weeks post‐OA induction. In addition, there was a significant (p<0.05) reduction of soleus muscle fiber cross‐sectional area at 4 and 8 weeks of OA‐induced groups compared to their relative controls; however, the muscle fiber atrophy was more pronounced at 4 weeks compared to 8 weeks. Moreover, there was a significant reduction in the mean values of percent weight borne on the injured hind limb for the OA‐induced group compared to the saline group throughout the study period (p<0.05). Interestingly, pain response significantly reversed at 8 weeks compared to 4 weeks (p<0.001), suggesting that this reversal in pain response could be the contributing factor on alleviation of soleus muscle atrophy under chronic OA pain. These results suggested that at 4 weeks post‐MIA injection is sufficient and suitable period to investigate OA‐related pain, IFP fibrosis and muscle atrophy. Taken together, a MIA‐induced OA rat can be used as a representative model in translational research to understand IFP fibrosis and hind limb muscle atrophy in OA as an integrated musculoskeletal disease.