Objective: The aim of this animal study was to investigate the short and long-term local histomorphologic effects and the utility of intra-articular application of ibuprofen. Methods: Forty-six Wistar Albino rats were used in the study. The rats were randomized into 5 groups of 8 and a sham group of 6. The 40 rats in the study groups were anaesthetised with 60 mg/kg of ketamine, then 0.25 ml ibuprofen (25 mg) was injected to the right knee joint of each rat (ibuprofen group) and 0.25 ml 0.9% saline to the left knee joint as the control group. To the 6 rats in the sham group, only puncture was applied to both knee joints. The rats in each of the 5 study groups were sacrificed on days 1, 2, 7, 14 and 21 respectively. The histomorphologic changes were graded on a 6point scale regarding inflammation of the synovia, cartilage tissue, and subchondral bone. Inflammation scores were compared using the Mann Whitney U-test and comparisons of the sacrifice day and drug used were evaluated with the Kruskal Wallis test. The p values below 0.05 were considered as significant. Results: Statistically significant difference was found between the ibuprofen injected knees (10/40) and the saline injected (0/40) and sham knees (0/12) in respect of hematoma positivity (p ¼ 0.002). Significantly higher inflammation scores were found in ibuprofen injected knees on the 1st, 2nd, 7th and 14th days compared to controls and sham (p < 0.05). Inflammation scores were similar in ibuprofen injected knees with and without hematoma (p > 0.05). Inflammation of the ibuprofen injected group was most severe on day one and the severity of inflammation reduced gradually throughout the 3 weeks. Conclusion: Our results show that intra-articular injection of ibuprofen can cause intra-articular hematoma. It also leads to transient inflammation of the synovia that is more severe in the early period, which gradually recovers.