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Summary Objective This review focuses on histomorphometry for assessing the pathological changes in various compartments of the joint including cartilage, bone and synovium in animal models of osteoarthritis (OA). Methods Different methodological approaches are presented concerning sampling, embedding, sectioning, staining, mounting of stained sections and measurement of histomorphometric parameters using automated and semi-automated methods. Notes are provided describing some methods in greater detail. Results Histomorphometry allows a significant gain of objectivity, accuracy and reproducibility in the quantification of the main histological parameters which best characterize OA in the affected joint (cartilage thickness (CT), chondrocyte size and density, cartilage fissure, proteoglycan (PG) content, subchondral bone plate thickness (SBPT), thickness of synovial living cell layer) in animal models. Conclusion Use of histomorphometry could contribute to a better quantification of histological differences between control and OA animals. Contributing also to the introduction of normative data, it is a major advantage for therapeutic assessments in experimental OA and particularly for the analytical comparison of the efficacy of disease modifying OA drugs (DMOAD).