Purpose: Increasing evidence suggests that low-grade chronic inflammation plays an important role in the progression of osteoarthritis (OA). However, the timing and dynamics of the inflammatory response in OA remain unclear. The initiation and development of joint inflammation are orchestrated by many cell types and various inflammatory mediators. Understanding these cellular and molecular kinetics should enable the identification of the time window of early intervention to arrest or slow down the progression of the disease. In this study, we aim to investigate the dynamics of inflammation and its resolution in the OA mouse model to provide new insights into the development of OA inflammation and to apply this knowledge in preclinical intervention studies. Methods: We established the collagenase-induced OA mouse model by intra-articular injection of collagenase in the knee of 8-week-old male mice. We set a series of time points, including day 1, 3, 7, 10, 14, 17, 21, 24, 28, and 31 after collagenase injection to investigate the kinetics of inflammation. At each time point, joint swelling was measured and knee samples were harvested for histological analyses. Cartilage damage was assessed by hematoxylin-safranin-O staining of knee sections. Synovial infiltration, hyperplasia and fibrosis were analyzed by hematoxylin and eosin staining of knee sections. Since neutrophil influx and phagocytic clearance by macrophages are two important cellular events in inflammation and resolution, immunohistochemistry was performed to evaluate the kinetics of neutrophils (MPO) and macrophages (F4/80). Results: Knee swelling increased shortly after OA induction and reached a peak on day 3. After day 3, it gradually decreased and approached full recovery on day 31. There was a peak of synovial hyperplasia on day 3. The synovium inflammatory infiltration was severe at the beginning and decreased with time. After day 10 post-induction, the knees injected with collagenase showed much higher scores of synovial fibrosis compared with control and increased with time, indicating the late stage of resolution that is associated with remodeling reaction. The immunohistochemistry analysis for neutrophils showed a peak on day 1. The immunohistochemistry staining for macrophages indicated much more positive staining of F4/80 on day 3 and day 7, which suggests that the extent of inflammation reached its peak in the day 1-3 time window and gradually subsided after day 3-7. Conclusions: Our preliminary results demonstrate that investigating the dynamics of inflammation in mouse model provides a method to understand the progression of OA inflammation and to define a window for preclinical intervention studies. In the collagenase-induced OA model, we mapped the initiation, peak, subsiding of inflammation and recovery over 31 days of observation and demonstrated the dynamics of neutrophils and macrophages.